Molecular Cell Biology

Front Matter
	Cover Page
	Halftitle Page
	About the Authors
	Title Page
	Copyright Page
	Dedication Page
	Preface
	Media and Supplements
	Acknowledgments
	Contents in Brief
	Contents
Part I Chemical and Molecular Foundations
	1 Molecules, Cells, and Model Organisms
		1.1 The Molecules of Life
			Proteins Give Cells Structure and Perform Most Cellular Tasks
			Nucleic Acids Carry Coded Information for Making Proteins at the Right Time and Place
			Phospholipids Are the Conserved Building Blocks of All Cellular Membranes
		1.2 Prokaryotic Cell Structure and Function
			Prokaryotes Comprise Two Kingdoms: Archaea and Eubacteria
			Escherichia coli Is Widely Used in Biological Research
		1.3 Eukaryotic Cell Structure and Function
			The Cytoskeleton Has Many Important Functions
			The Nucleus Contains the DNA Genome, RNA Synthetic Apparatus, and a Fibrous Matrix
			Eukaryotic Cells Contain a Large Number of Internal Membrane Structures
			Mitochondria are the Principal Sites of ATP Production in Aerobic Cells
			Chloroplasts Contain Internal Compartments in Which Photosynthesis Takes Place
			All Eukaryotic Cells Use a Similar Cycle to Regulate Their Division
		1.4 Unicellular Eukaryotic Model Organisms
			Yeasts Are Used to Study Fundamental Aspects of Eukaryotic Cell Structure and Function
			Mutations in Yeast Led to the Identification of Key Cell Cycle Proteins
			Studies in the Alga Chlamydomonas Reinhardtii Led to the Development of a Powerful Technique to Study Brain Function
			The Parasite That Causes Malaria Has Novel Organelles That Allow It to Undergo a Remarkable Life Cycle
		1.5 Metazoan Structure, Differentiation, and Model Organisms
			Multicellularity Requires Cell-Cell and Cell-Matrix Adhesions
			Epithelia Originated Early in Evolution
			Tissues Are Organized into Organs
			Genomics Has Revealed Important Aspects of Metazoan Evolution and Cell Function
			Embryonic Development Uses a conserved Set of Master Transcription Factors
			Planaria Are Used to Study Stem Cells and Tissue Regeneration
			Invertebrates, Fish, Mice, and Other Organisms Serve as Experimental Systems for Study of Human Development and Disease
			Genetic Diseases Elucidate Important Aspects of Cell Function
			The Following Chapters Present Much Experimental Data That Explains How We Know What We Know About Cell Structure and Function
	2 Chemical Foundations
		2.1 Covalent Bonds and Noncovalent Interactions
			The Electronic Structure of an Atom Determines the Number and Geometry of the Covalent Bonds It Can Make
			Electrons May Be Shared Equally or Unequally in Covalent Bonds
			Covalent Bonds Are Much Stronger and More Stable Than Noncovalent Interactions
			Ionic Interactions Are Attractions Between Oppositely Charged Ions
			Hydrogen Bonds Are Noncovalent Interactions That Determine the Water Solubility of Uncharged Molecules
			Van der Waals Interactions Are Weak Attractive Interactions Caused by Transient Dipoles
			The Hydrophobic Effect Causes Nonpolar Molecules to Adhere to One Another
			Molecular Complementarity Due to Noncovalent Interactions Leads to a Lock-and-Key Fit Between Biomolecules
		2.2 Chemical Building Blocks of Cells
			Amino Acids Differing Only in Their Side Chains Compose Proteins
			Five Different Nucleotides Are Used to Build Nucleic Acids
			Monosaccharides Covalently Assemble into Linear and Branched Polysaccharides
			Phospholipids Associate Noncovalently to Form the Basic Bilayer Structure of Biomembranes
		2.3 Chemical Reactions and Chemical Equilibrium
			A Chemical Reaction Is in Equilibrium When the Rates of the Forward and Reverse Reactions Are Equal
			The Equilibrium Constant Reflects the Extent of a Chemical Reaction
			Chemical Reactions in Cells Are at Steady State
			Dissociation Constants of Binding Reactions Reflect the Affinity of Interacting Molecules
			Biological Fluids Have Characteristic pH Values
			Hydrogen Ions Are Released by Acids and Taken Up by Bases
			Buffers Maintain the pH of Intracellular and Extracellular Fluids
		2.4 Biochemical Energetics
			Several Forms of Energy Are Important in Biological Systems
			Cells Can Transform One Type of Energy Into Another
			The Change in Free Energy Determines If a Chemical Reaction Will Occur Spontaneously
			The ΔG°′ of a Reaction Can Be Calculated from Its Keq
			The Rate of a Reaction Depends on the Activation Energy Necessary to Energize the Reactants into a Transition State
			Life Depends on the Coupling of Unfavorable Chemical Reactions with Energetically Favorable Ones
			Hydrolysis of ATP Releases Substantial Free Energy and Drives Many Cellular Processes
			ATP Is Generated During Photosynthesis and Respiration
			NAD+ and FAD Couple Many Biological Oxidation and Reduction Reactions
	3 Protein Structure and Function
		3.1 Hierarchical Structure of Proteins
			The Primary Structure of a Protein Is Its Linear Arrangement of Amino Acids
			Secondary Structures Are the Core Elements of Protein Architecture
			Tertiary Structure Is the Overall Folding of a Polypeptide Chain
			There Are Four Broad Structural Categories of Proteins
			Different Ways of Depicting the Conformation of Proteins Convey Different Types of Information
			Structural Motifs Are Regular Combinations of Secondary Structures
			Domains Are Modules of Tertiary Structure
			Multiple Polypeptides Assemble into Quaternary Structures and Supramolecular Complexes
			Comparing Protein Sequences and Structures Provides Insight into Protein Function and Evolution
		3.2 Protein Folding
			Planar Peptide Bonds Limit the Shapes into Which Proteins Can Fold
			The Amino Acid Sequence of a Protein Determines How It Will Fold
			Folding of Proteins in Vivo Is Promoted by Chaperones
			Protein Folding Is Promoted by Proline Isomerases
			Abnormally Folded Proteins Can Form Amyloids That Are Implicated in Diseases
		3.3 Protein Binding and Enzyme Catalysis
			Specific Binding of Ligands Underlies the Functions of Most Proteins
			Enzymes Are Highly Efficient and Specific Catalysts
			An Enzyme’s Active Site Binds Substrates and Carries Out Catalysis
			Serine Proteases Demonstrate How an Enzyme’s Active Site Works
			Enzymes in a Common Pathway Are Often Physically Associated with One Another
		3.4 Regulating Protein Function
			Regulated Synthesis and Degradation of Proteins Is a Fundamental Property of Cells
			The Proteasome Is a Molecular Machine Used to Degrade Proteins
			Ubiquitin Marks Cytosolic Proteins for Degradation in Proteasomes
			Noncovalent Binding Permits Allosteric, or Cooperative, Regulation of Proteins
			Noncovalent Binding of Calcium and GTP Are Widely Used as Allosteric Switches to Control Protein Activity
			Phosphorylation and Dephosphorylation Covalently Regulate Protein Activity
			Ubiquitinylation and Deubiquitinylation Covalently Regulate Protein Activity
			Proteolytic Cleavage Irreversibly Activates or Inactivates Some Proteins
			Higher-Order Regulation Includes Control of Protein Location
		3.5 Purifying, Detecting, and Characterizing Proteins
			Centrifugation Can Separate Particles and Molecules That Differ in Mass or Density
			Electrophoresis Separates Molecules on the Basis of Their Charge-to-Mass Ratio
			Liquid Chromatography Resolves Proteins by Mass, Charge, or Affinity
			Highly Specific Enzyme and Antibody Assays Can Detect Individual Proteins
			Radioisotopes Are Indispensable Tools for Detecting Biological Molecules
			Mass Spectrometry Can Determine the Mass and Sequence of Proteins
			Protein Primary Structure Can Be Determined by Chemical Methods and from Gene Sequences
			Protein Conformation Is Determined by Sophisticated Physical Methods
		3.6 Proteomics
			Proteomics Is the Study of All or a Large Subset of Proteins in a Biological System
			Advanced Techniques in Mass Spectrometry Are Critical to Proteomic Analysis
	4 Culturing and Visualizing Cells
		4.1 Growing and Studying Cells in Culture
			Culture of Animal Cells Requires Nutrient-Rich Media and Special Solid Surfaces
			Primary Cell Cultures and Cell Strains Have a Finite Life Span
			Transformed cells can Grow Indefinitely in Culture
			Flow cytometry Separates Different Cell Types
			Growth of cells in Two-Dimensional and Three-Dimensional culture Mimics the In Vivo Environment
			Hybridomas Produce Abundant Monoclonal Antibodies
			A Wide Variety of cell Biological Processes can Be Studied with Cultured Cells
			Drugs are commonly Used in cell Biological Research
		4.2 Light Microscopy: ExploringCell Structure and Visualizing Proteins Within Cells
			The Resolution of the conventional light Microscope Is about 0.2 μm
			Phase-contrast and Differential-Interference-contrast Microscopy Visualize Unstained live cells
			Imaging Subcellular Details Often requires That Specimens Be fixed, Sectioned, and Stained
			Fluorescence Microscopy can localize and Quantify Specific Molecules in live cells
			Intracellular Ion concentrations can Be Determined with Ion-Sensitive fluorescent Dyes
			Immunofluorescence Microscopy can Detect Specific Proteins in fixed cells
			Tagging with fluorescent Proteins allows the Visualization of Specific Proteins in live cells
			Deconvolution and confocal Microscopy Enhance Visualization of Three-Dimensional fluorescent Objects
			Two-Photon Excitation Microscopy allows Imaging Deep into Tissue Samples
			TIRF Microscopy Provides Exceptional Imaging in One focal Plane
			FRAP reveals the Dynamics of cellular components
			FRET Measures Distance Between fluorochromes
			Super-resolution Microscopy can localize Proteins to Nanometer accuracy
			Light-Sheet Microscopy can rapidly Image cells in living Tissue
		4.3 Electron Microscopy:High?Resolution Imaging
			Single Molecules or Structures can Be Imaged Using a Negative Stain or Metal Shadowing
			Cells and Tissues are cut into Thin Sections for Viewing by Electron Microscopy
			Immunoelectron Microscopy Localizes Proteins at the Ultrastructural Level
			Cryoelectron Microscopy Allows Visualization of Specimens Without Fixation or Staining
			Scanning Electron Microscopy of Metal-coated Specimens reveals Surface Features
		4.4 Isolation of Cell Organelles
			Disruption of cells releases Their Organelles and Other contents
			Centrifugation can Separate Many Types of Organelles
			Organelle-Specific antibodies are Useful in Preparing Highly Purified Organelles
			Proteomics reveals the Protein composition of Organelles
Part II Biomembranes, Genes, and Gene Regulation
	5 Fundamental Molecular Genetic Mechanisms
		5.1 Structure of Nucleic Acids
			A Nucleic acid Strand Is a linear Polymer with End-to-End Directionality
			Native DNA Is a Double Helix of complementary antiparallel Strands
			DNA can Undergo reversible Strand Separation
			Torsional Stress in DNa Is relieved by Enzymes
			Different Types of rNa Exhibit Various conformations related to Their functions
		5.2 Transcription of Protein-Coding Genes and Formation of Functional mRNA
			A Template DNa Strand Is Transcribed into a complementary rNa chain by rNa Polymerase
			Organization of Genes Differs in Prokaryotic and Eukaryotic DNa
			Eukaryotic Precursor mrNas are Processed to form functional mrNas
			Alternative rNa Splicing Increases the Number of Proteins Expressed from a Single Eukaryotic Gene
		5.3 The Decoding of mRNA by tRNAs
			Messenger rNa carries Information from DNa in a Three-letter Genetic code
			The folded Structure of trNa Promotes Its Decoding functions
			Nonstandard Base Pairing Often Occurs Between codons and anticodons
			Amino Acids Become Activated When Covalently Linked to tRNAs
		5.4 Stepwise Synthesis of Proteinson Ribosomes
			Ribosomes are Protein-Synthesizing Machines
			Methionyl-trNaiMet recognizes the aUG Start codon
			Eukaryotic Translation Initiation Usually Occurs at the first aUG Downstream from the 5′ End of an mrNa
			During Chain Elongation Each Incoming aminoacyl-trNa Moves Through Three ribosomal Sites
			Translation Is Terminated by release factors When a Stop codon Is reached
			Polysomes and rapid ribosome recycling Increase the Efficiency of Translation
			GTPase-Superfamily Proteins function in Several Quality-control Steps of Translation
			Nonsense Mutations cause Premature Termination of Protein Synthesis
		5.5 DNA Replication
			DNA Polymerases require a Primer to Initiate replication
			Duplex DNa Is Unwound, and Daughter Strands are formed at the DNa replication fork
			Several Proteins Participate in DNa replication
			DNA replication Occurs Bidirectionally from Each Origin
		5.6 DNA Repair and Recombination
			DNA Polymerases Introduce copying Errors and also correct Them
			Chemical and radiation Damage to DNa can lead to Mutations
			High-fidelity DNa Excision-repair Systems recognize and repair Damage
			Base Excision repairs T-G Mismatches and Damaged Bases
			Mismatch Excision repairs Other Mismatches and Small Insertions and Deletions
			Nucleotide Excision repairs chemical adducts that Distort Normal DNa Shape
			Two Systems Use recombination to repair Double-Strand Breaks in DNa
			Homologous recombination can repair DNa Damage and Generate Genetic Diversity
		5.7 Viruses: Parasites of the CellularGenetic System
			Most Viral Host Ranges are Narrow
			Viral capsids are regular arrays of One or a few Types of Protein
			Viruses can Be cloned and counted in Plaque Assays
			Lytic Viral Growth cycles lead to Death of Host Cells
			Viral DNA Is Integrated into the Host-cell Genome in Some Nonlytic Viral Growth Cycles
	6 Molecular Genetic Techniques
		6.1 Genetic Analysis of Mutations to Identify and Study Genes
			Recessive and Dominant Mutant alleles Generally Have Opposite Effects on Gene function
			Segregation of Mutations in Breeding Experiments reveals Their Dominance or recessivity
			Conditional Mutations can Be Used to Study Essential Genes in Yeast
			Recessive lethal Mutations in Diploids can Be Identified by Inbreeding and Maintained in Heterozygotes
			Complementation Tests Determine Whether Different recessive Mutations are in the Same Gene
			Double Mutants are Useful in assessing the Order in Which Proteins function
			Genetic Suppression and Synthetic lethality can reveal Interacting or redundant Proteins
			Genes can Be Identified by Their Map Position on the chromosome
		6.2 DNA Cloning and Characterization
			Restriction Enzymes and DNa ligases allow Insertion of DNa fragments into cloning Vectors
			Isolated DNa fragments can Be cloned into E. coli Plasmid Vectors
			Yeast Genomic libraries can Be constructed with Shuttle Vectors and Screened by Functional Complementation
			cDNA Libraries Represent the Sequences of Protein-Coding Genes
			The Polymerase chain reaction amplifies a Specific DNa Sequence from a complex Mixture
			Cloned DNa Molecules can Be Sequenced rapidly by Methods Based on Pcr
		6.3 Using Cloned DNA Fragments to Study Gene Expression
			Hybridization Techniques Permit Detection of Specific DNa fragments and mrNas
			DNA Microarrays can Be Used to Evaluate the Expression of Many Genes at One Time
			Cluster analysis of Multiple Expression Experiments Identifies co-regulated Genes
			E. coli Expression Systems can Produce Large Quantities of Proteins from Cloned Genes
			Plasmid Expression Vectors can Be Designed for Use in animal cells
		6.4 Locating and Identifying Human Disease Genes
			Monogenic Diseases Show One of Three Patterns of Inheritance
			DNA Polymorphisms are Used as Markers for linkage Mapping of Human Mutations
			Linkage Studies can Map Disease Genes with a resolution of about 1 centimorgan
			Further analysis Is Needed to locate a Disease Gene in cloned DNa
			Many Inherited Diseases result from Multiple Genetic Defects
		6.5 Inactivating the Function of Specific Genes in Eukaryotes
			Normal Yeast Genes can Be replaced with Mutant alleles by Homologous recombination
			Genes can Be Placed Under the control of an Experimentally regulated Promoter
			Specific Genes can Be Permanently Inactivated in the Germ line of Mice
			Somatic cell recombination can Inactivate Genes in Specific Tissues
			Dominant-Negative alleles can Inhibit the function of Some Genes
			RNA Interference causes Gene Inactivation by Destroying the corresponding mrNa
			Engineered CRISPR–cas9 Systems allow Precise Genome Editing
	7 Biomembrane Structure
		7.1 The Lipid Bilayer: Composition and Structural Organization
			Phospholipids Spontaneously form Bilayers
			Phospholipid Bilayers form a Sealed compartment Surrounding an Internal aqueous Space
			Biomembranes contain Three Principal classes of lipids
			Most lipids and Many Proteins are laterally Mobile in Biomembranes
			Lipid composition Influences the Physical Properties of Membranes
			Lipid composition Is Different in the Exoplasmic and cytosolic leaflets
			Cholesterol and Sphingolipids cluster with Specific Proteins in Membrane Microdomains
			Cells Store Excess lipids in lipid Droplets
		7.2 Membrane Proteins: Structure and Basic Functions
			Proteins Interact with Membranes in Three Different Ways
			Most Transmembrane Proteins Have Membrane-Spanning α Helices
			Multiple β Strands in Porins form Membrane-Spanning “Barrels”
			Covalently attached lipids anchor Some Proteins to Membranes
			All Transmembrane Proteins and Glycolipids are asymmetrically Oriented in the Bilayer
			Lipid-Binding Motifs Help Target Peripheral Proteins to the Membrane
			Proteins Can Be Removed from Membranes by Detergents or High-Salt Solutions
		7.3 Phospholipids, Sphingolipids, and Cholesterol: Synthesis and Intracellular Movement
			Fatty acids are assembled from Two-carbon Building Blocks by Several Important Enzymes
			Small cytosolic Proteins facilitate Movement of fatty acids
			Fatty acids are Incorporated into Phospholipids Primarily on the Er Membrane
			Flippases Move Phospholipids from One Membrane leaflet to the Opposite leaflet
			Cholesterol Is Synthesized by Enzymes in the cytosol and Er Membrane
			Cholesterol and Phospholipids are Transported Between Organelles by Several Mechanisms
	8 Genes, Genomics, and Chromosomes
		8.1 Eukaryotic Gene Structure
			Most Eukaryotic Genes contain Introns and Produce mrNas Encoding Single Proteins
			Simple and complex Transcription Units are found in Eukaryotic Genomes
			Protein-coding Genes May Be Solitary or Belong to a Gene family
			Heavily Used Gene Products are Encoded by Multiple copies of Genes
			Nonprotein-coding Genes Encode functional rNas
		8.2 Chromosomal Organization of Genes and Noncoding DNA
			Genomes of Many Organisms contain Nonfunctional DNa
			Most Simple-Sequence DNAs Are Concentrated in Specific Chromosomal Locations
			DNA Fingerprinting Depends on Differences in length of Simple-Sequence DNas
			Unclassified Intergenic DNa Occupies a Significant Portion of the Genome
		8.3 Transposable (Mobile) DNA Elements
			Movement of Mobile Elements Involves a DNA or an RNA Intermediate
			DNA Transposons are Present in Prokaryotes and Eukaryotes
			LTR Retrotransposons Behave Like Intracellular Retroviruses
			Non-LTR retrotransposons Transpose by a Distinct Mechanism
			Other retroposed rNas are found in Genomic DNA
			Mobile DNA Elements Have Significantly Influenced Evolution
		8.4 Genomics: Genome?Wide Analysisof Gene Structure and Function
			Stored Sequences Suggest functions of Newly Identified Genes and Proteins
			Comparison of related Sequences from Different Species can Give clues to Evolutionary relationships among Proteins
			Genes can Be Identified Within Genomic DNA Sequences
			The Number of Protein-coding Genes in an Organism’s Genome Is Not Directly related to Its Biological Complexity
		8.5 Structural Organization of Eukaryotic Chromosomes
			Chromatin Exists in Extended and Condensed Forms
			Modifications of Histone Tails Control Chromatin Condensation and Function
			Nonhistone Proteins Organize Long Chromatin Loops
			Additional Nonhistone Proteins Regulate Transcription and Replication
		8.6 Morphology and Functional Elements of Eukaryotic Chromosomes
			Chromosome Number, Size, and Shape at Metaphase are Species-Specific
			During Metaphase, chromosomes can Be Distinguished by Banding Patterns and chromosome Painting
			Chromosome Painting and DNA Sequencing Reveal the Evolution of chromosomes
			Interphase Polytene chromosomes arise by DNA Amplification
			Three functional Elements are required for replication and Stable Inheritance of chromosomes
			Centromere Sequences Vary Greatly in length and complexity
			Addition of Telomeric Sequences by Telomerase Prevents Shortening of chromosomes
	9 Transcriptional Control of Gene Expression
		9.1 Control of Gene Expression in Bacteria
			Transcription Initiation by Bacterial rNa Polymerase requires association with a Sigma factor
			Initiation of lac Operon Transcription can Be repressed or activated
			Small Molecules regulate Expression of Many Bacterial Genes via DNA-Binding repressors and activators
			Transcription Initiation from Some Promoters requires alternative Sigma factors
			Transcription by a54-rNa Polymerase Is controlled by activators That Bind far from the Promoter
			Many Bacterial responses are controlled by Two-component regulatory Systems
			Expression of Many Bacterial Operons Is controlled by regulation of Transcriptional Elongation
		9.2 Overview of Eukaryotic Gene Control
			Regulatory Elements in Eukaryotic DNA are found Both close to and Many Kilobases away from Transcription Start Sites
			Three Eukaryotic rNa Polymerases catalyze formation of Different rNas
			The largest Subunit in rNa Polymerase II Has an Essential carboxy-Terminal repeat
		9.3 RNA Polymerase II Promoters and General Transcription Factors
			RNA Polymerase II Initiates Transcription at DNA Sequences corresponding to the 5′ cap of mRNAs
			The TATA Box, Initiators, and cpG Islands function as Promoters in Eukaryotic DNA
			General Transcription factors Position RNA Polymerase II at Start Sites and assist in Initiation
			Elongation factors regulate the Initial Stages of Transcription in the Promoter-Proximal region
		9.4 Regulatory Sequences in Protein-Coding Genes and the Proteins Through Which They Function
			Promoter-Proximal Elements Help regulate Eukaryotic Genes
			Distant Enhancers Often Stimulate Transcription by RNA Polymerase II
			Most Eukaryotic Genes are regulated by Multiple Transcription-control Elements 379
			DNAse I footprinting and EMSa Detect Protein-DNA Interactions
			Activators Are Composed of Distinct Functional Domains
			Repressors Are the Functional Converse of Activators
			DNA-Binding Domains can Be classified into Numerous Structural Types
			Structurally Diverse activation and repression Domains regulate Transcription
			Transcription factor Interactions Increase Gene-control Options
			Multiprotein complexes form on Enhancers
		9.5 Molecular Mechanisms of TranscriptionRepression and Activation
			Formation of Heterochromatin Silences Gene Expression at Telomeres, near centromeres, and in Other Regions
			Repressors Can Direct Histone Deacetylation at Specific Genes
			Activators can Direct Histone acetylation at Specific Genes
			Chromatin-Remodeling Complexes Help Activate or Repress Transcription
			Pioneer Transcription factors Initiate the Process of Gene Activation During cellular Differentiation
			The Mediator complex forms a Molecular Bridge Between Activation Domains and Pol II
		9.6 Regulation of Transcription-Factor Activity
			DNAse I Hypersensitive Sites reflect the Developmental History of cellular Differentiation
			Nuclear receptors are regulated by Extracellular Signals
			All Nuclear receptors Share a common Domain Structure
			Nuclear-Receptor Response Elements Contain Inverted or Direct Repeats
			Hormone Binding to a Nuclear receptor regulates Its activity as a Transcription Factor
			Metazoans regulate the RNA Polymerase II Transition from Initiation to Elongation
			Termination of Transcription Is Also Regulated
		9.7 Epigenetic Regulation of Transcription
			DNA Methylation represses Transcription
			Methylation of Specific Histone lysines Is linked to Epigenetic Mechanisms of Gene repression
			Epigenetic control by Polycomb and Trithorax complexes
			Long Noncoding RNAs Direct Epigenetic Repression in Metazoans
		9.8 Other Eukaryotic Transcription Systems
			Transcription Initiation by Pol I and Pol III Is analogous to That by Pol II
	10 Post-transcriptional Gene Control
		10.1 Processing of Eukaryotic Pre-mRNA
			The 5′ cap Is added to Nascent RNAs Shortly after Transcription Initiation
			A Diverse Set of Proteins with conserved RNA-Binding Domains associate with Pre-mRNAs
			Splicing Occurs at Short, conserved Sequences in Pre-mRNAs via Two Transesterification reactions
			During Splicing, snRNAs Base-Pair with Pre-mRNA
			Spliceosomes, assembled from snRNP s and a Pre-mRNA, carry Out Splicing
			Chain Elongation by RNA Polymerase II Is coupled to the Presence of RNA-Processing factors
			SR Proteins contribute to Exon Definition in long Pre-mRNAs
			Self-Splicing Group II Introns Provide clues to the Evolution of snRNAs
			3′ Cleavage and Polyadenylation of Pre-mRNAs are Tightly coupled
			Nuclear Exoribonucleases Degrade RNA That Is Processed Out of Pre-mRNAs
			RNA Processing Solves the Problem of Pervasive Transcription of the Genome in Metazoans
		10.2 Regulation of Pre-mRNA Processing
			Alternative Splicing Generates Transcripts with Different combinations of Exons
			A cascade of regulated RNA Splicing controls Drosophila Sexual Differentiation
			Splicing repressors and activators control Splicing at alternative Sites
			RNA Editing alters the Sequences of Some Pre-mRNAs
		10.3 Transport of mRNA Across the Nuclear Envelope
			Phosphorylation and Dephosphorylation of Sr Proteins Imposes Directionality on mrNP Export across the Nuclear Pore Complex
			Balbiani rings in Insect larval Salivary Glands allow Direct Visualization of mrNP Export Through NPcs
			Pre-mRNAs in Spliceosomes are Not Exported from the Nucleus
			HIV Rev Protein regulates the Transport of Unspliced Viral mRNAs
		10.4 Cytoplasmic Mechanisms of Post-transcriptional Control
			Degradation of mRNAs in the cytoplasm Occurs by Several Mechanisms
			Adenines in mRNAs and lncRNAs May Be Post-transcriptionally Modified by N6 Methylation
			Micro-RNAs repress Translation and Induce Degradation of Specific mRNAs
			Alternative Polyadenylation Increases miRNA control Options
			RNA Interference Induces Degradation of Precisely complementary mRNAs
			Cytoplasmic Polyadenylation Promotes Translation of Some mRNAs
			Protein Synthesis can Be Globally regulated
			Sequence-Specific RNA-Binding Proteins control Translation of Specific mRNAs
			Surveillance Mechanisms Prevent Translation of Improperly Processed mRNAs
			Localization of mRNAs Permits Production of Proteins at Specific regions Within the cytoplasm
		10.5 Processing of rRNA and tRNA
			Pre-rRNA Genes function as Nucleolar Organizers
			Small Nucleolar RNAs assist in Processing Pre-rRNAs
			Self-Splicing Group I Introns Were the first Examples of catalytic RNA
			Pre-tRNAs Undergo Extensive Modification in the Nucleus
			Nuclear Bodies are functionally Specialized Nuclear Domains
Part III Cellular Organization and Function
	11 Transmembrane Transport of Ions and Small Molecules
		11.1 Overview of Transmembrane Transport
			Only Gases and Small Uncharged Molecules Cross Membranes by Simple Diffusion 474
			Three Main classes of Membrane Proteins Transport Molecules and Ions across cellular Membranes
		11.2 Facilitated Transport of Glucose and Water
			Uniport Transport Is faster and More Specific than Simple Diffusion
			The low Km of the GlUT1 Uniporter Enables It to Transport Glucose into Most Mammalian Cells
			The Human Genome Encodes a family of Sugar-Transporting GLUT Proteins
			Transport Proteins can Be Studied Using Artificial Membranes and recombinant cells
			Osmotic Pressure causes Water to Move Across Membranes
			Aquaporins Increase the Water Permeability of cellular Membranes
		11.3 ATP-Powered Pumps and the Intracellular Ionic Environment
			There are four Main classes of aTP-Powered Pumps
			ATP-Powered Ion Pumps Generate and Maintain Ionic Gradients across cellular Membranes
			Muscle Relaxation Depends on Ca2+ ATPases That Pump CA2+ from the cytosol into the Sarcoplasmic Reticulum
			The Mechanism of action of the Ca2+ Pump Is Known in Detail
			Calmodulin regulates the Plasma-Membrane Pumps That Control Cytosolic Ca2+ Concentrations
			The Na+/K+ aTPase Maintains the Intracellular Na+ and K+ concentrations in Animal Cells
			V-class H+ aTPases Maintain the acidity of lysosomes and Vacuoles
			ABC Proteins Export a Wide Variety of Drugs and Toxins from the Cell
			Certain ABC Proteins “flip” Phospholipids and Other Lipid-Soluble Substrates from One Membrane leaflet to the Other
			The ABC cystic fibrosis Transmembrane regulator Is a chloride channel, Not a Pump
		11.4 Nongated Ion Channels and the Resting Membrane Potential
			Selective Movement of Ions creates a Transmembrane Electric Gradient
			The resting Membrane Potential in Animal Cells Depends largely on the Outward flow of K+ Ions Through Open K+ Channels
			Ion channels are Selective for certain Ions by Virtue of a Molecular “Selectivity filter”
			Patch clamps Permit Measurement of Ion Movements Through Single channels
			Novel Ion channels can Be characterized by a combination of Oocyte Expression and Patch Clamping
		11.5 Cotransport by Symporters and Antiporters
			Na+ Entry into Mammalian Cells Is Thermodynamically Favored
			Na+-linked Symporters Enable animal cells to Import Glucose and amino acids against High concentration Gradients
			A Bacterial Na+/amino acid Symporter reveals How Symport Works
			A Na+-linked ca2+ antiporter regulates the Strength of Cardiac Muscle Contraction
			Several cotransporters regulate cytosolic pH
			An Anion antiporter Is Essential for Transport of CO2 by Erythrocytes
			Numerous Transport Proteins Enable Plant Vacuoles to accumulate Metabolites and Ions
		11.6 Transcellular Transport
			Multiple Transport Proteins are Needed to Move Glucose and amino acids across Epithelia
			Simple rehydration Therapy Depends on the Osmotic Gradient created by absorption of Glucose and Na+
			Parietal cells acidify the Stomach contents While Maintaining a Neutral cytosolic pH
			Bone resorption requires the coordinated function of a V-class Proton Pump and a Specific chloride channel
	12 Cellular Energetics
		12.1 First Step of Harvesting Energy from Glucose: Glycolysis
			During Glycolysis (Stage I), cytosolic Enzymes convert Glucose to Pyruvate
			The rate of Glycolysis Is adjusted to Meet the cell’s Need for aTP
			Glucose Is fermented When Oxygen Is Scarce
		12.2 The Structure and Functions ofMitochondria
			Mitochondria are Multifunctional Organelles
			Mitochondria Have Two Structurally and functionally Distinct Membranes
			Mitochondria contain DNA located in the Matrix
			The Size, Structure, and coding capacity of mtDNA Vary considerably among Organisms
			Products of Mitochondrial Genes are Not Exported
			Mitochondria Evolved from a Single Endosymbiotic Event Involving a Rickettsia-like Bacterium
			Mitochondrial Genetic codes Differ from the Standard Nuclear Code
			Mutations in Mitochondrial DNA Cause Several Genetic Diseases in Humans
			Mitochondria Are Dynamic Organelles That Interact Directly With One Another
			Mitochondria are Influenced by Direct contacts with the Endoplasmic Reticulum
		12.3 The Citric Acid Cycle and Fatty Acid Oxidation
			In the First Part of Stage II, Pyruvate Is Converted to Acetyl CoA and High-Energy Electrons
			In the Second Part of Stage II, the Citric Acid Cycle Oxidizes the Acetyl Group in Acetyl CoA to CO2 and Generates High-Energy Electrons
			Transporters in the Inner Mitochondrial Membrane Help Maintain Appropriate Cytosolic and Matrix Concentrations of NAD+ and NADH
			Mitochondrial Oxidation of Fatty Acids Generates ATP
			Peroxisomal Oxidation of Fatty Acids Generates No ATP
		12.4 The Electron-Transport Chain and Generation of the Proton-Motive Force
			Oxidation of NADH and FADH2 Releases a Significant Amount of Energy
			Electron Transport in Mitochondria Is coupled to Proton Pumping
			Electrons Flow “Downhill” Through a Series of Electron carriers
			Four Large Multiprotein Complexes Couple Electron Transport to Proton Pumping Across the Inner Mitochondrial Membrane
			The Reduction Potentials of Electron Carriers in the Electron-Transport Chain Favor Electron Flow From NADH to O2
			The Multiprotein Complexes of the Electron-Transport Chain Assemble into Supercomplexes
			Reactive Oxygen Species Are By-Products of Electron Transport
			Experiments Using Purified Electron-Transport Chain Complexes Established the Stoichiometry of Proton Pumping
			The Proton-Motive Force in Mitochondria Is Due Largely to a Voltage Gradient Across the Inner Membrane
		12.5 Harnessing the Proton-Motive Force to Synthesize ATP
			The Mechanism of ATP Synthesis Is Shared Among Bacteria, Mitochondria, and Chloroplasts
			ATP Synthase comprises F0 and F1 Multiprotein Complexes
			Rotation of the F1γ Subunit, Driven by Proton Movement Through F0, Powers ATP Synthesis
			Multiple Protons Must Pass Through ATP Synthase to Synthesize One ATP
			F0c Ring Rotation Is Driven by Protons Flowing Through Transmembrane Channels
			ATP-ADP Exchange Across the Inner Mitochondrial Membrane Is Powered by the Proton-Motive force
			The Rate of Mitochondrial Oxidation Normally Depends on ADP levels
			Mitochondria in Brown Fat Use the Proton-Motive Force to Generate Heat
		12.6 Photosynthesis and Light-Absorbing Pigments
			Thylakoid Membranes in chloroplasts Are the Sites of Photosynthesis in Plants
			Chloroplasts Contain Large DNAs Often Encoding More Than a Hundred Proteins
			Three of the Four Stages in Photosynthesis Occur Only During Illumination
			Photosystems Comprise a Reaction Center and Associated Light-Harvesting Complexes
			Photoelectron Transport from Energized Reaction-Center Chlorophyll a Produces a Charge Separation
			Internal Antennas and Light-Harvesting Complexes Increase the Efficiency of Photosynthesis
		12.7 Molecular Analysis of Photosystems
			The Single Photosystem of Purple Bacteria Generates a Proton-Motive force but No O2
			Chloroplasts Contain Two Functionally and Spatially Distinct Photosystems
			Linear Electron Flow Through Both Plant Photosystems Generates a Proton-Motive Force, O2, and NADPH
			An Oxygen-Evolving Complex Is Located on the Luminal SUrface of the PSII Reaction Center
			Multiple Mechanisms Protect Cells Against Damage From Reactive Oxygen Species During Photoelectron Transport
			Cyclic Electron Flow Through PSI Generates a Proton-Motive Force but No NADPH or O2
			Relative Activities of Photosystems I and II Are Regulated
		12.8 CO2 Metabolism During Photosynthesis
			Rubisco Fixes CO2 in the Chloroplast Stroma
			Synthesis of Sucrose Using Fixed CO2 Is Completed in the Cytosol
			Light and Rubisco Activase Stimulate CO2 Fixation
			Photorespiration Competes with Carbon Fixation and Is Reduced in C4 Plants
	13 Moving Proteins into Membranes and Organelles
		13.1 Targeting Proteins To and Acrossthe ER Membrane
			Pulse-Chase Experiments with Purified Er Membranes Demonstrated That Secreted Proteins Cross the ER Membrane
			A Hydrophobic N-Terminal Signal Sequence Targets Nascent Secretory Proteins to the Er
			Cotranslational Translocation Is Initiated by Two GTP-Hydrolyzing Proteins
			Passage of Growing Polypeptides Through the Translocon Is Driven by Translation
			ATP Hydrolysis Powers Post-translational Translocation of Some Secretory Proteins in Yeast
		13.2 Insertion of Membrane Proteins into the ER
			Several Topological Classes of Integral Membrane Proteins Are Synthesized on the ER
			Internal Stop-Transfer Anchor and Signal-Anchor Sequences Determine Topology of Single-Pass Proteins
			Multipass Proteins Have Multiple Internal Topogenic Sequences
			A Phospholipid Anchor Tethers Some Cell-Surface Proteins to the Membrane
			The Topology of a Membrane Protein Can Often Be Deduced from Its Sequence
		13.3 Protein Modifications, Folding, and Quality Control in the ER
			A Preformed N-linked Oligosaccharide Is added to Many Proteins in the Rough Er
			Oligosaccharide Side chains May Promote folding and Stability of Glycoproteins
			Disulfide Bonds Are Formed and Rearranged by Proteins in the ER Lumen
			Chaperones and Other Er Proteins Facilitate Folding and Assembly of Proteins
			Improperly Folded Proteins in the ER Induce Expression of Protein-Folding Catalysts
			Unassembled or Misfolded Proteins in the ER Are Often Transported to the cytosol for Degradation
		13.4 Targeting of Proteins to Mitochondria and Chloroplasts
			Amphipathic N-Terminal Targeting Sequences Direct Proteins to the Mitochondrial Matrix
			Mitochondrial Protein Import Requires Outer-Membrane Receptors and Translocons in Both Membranes
			Studies with Chimeric Proteins Demonstrate Important Features of Mitochondrial Protein Import
			Three Energy Inputs Are Needed to Import Proteins into Mitochondria
			Multiple Signals and Pathways Target Proteins to Submitochondrial Compartments
			Import of Chloroplast Stromal Proteins Is Similar to Import of Mitochondrial Matrix Proteins
			Proteins Are Targeted to Thylakoids by Mechanisms Related to Bacterial Protein Translocation
		13.5 Targeting of Peroxisomal Proteins
			A cytosolic receptor Targets Proteins with an SKL Sequence at the c-Terminus to the Peroxisomal Matrix
			Peroxisomal Membrane and Matrix Proteins Are Incorporated by Different Pathways
		13.6 Transport Into and Out of the Nucleus
			Large and Small Molecules Enter and Leave the Nucleus via Nuclear Pore Complexes
			Nuclear Transport Receptors Escort Proteins Containing Nuclear-Localization Signals into the Nucleus
			A Second Type of Nuclear Transport Receptor Escorts Proteins Containing Nuclear-Export Signals Out of the Nucleus
			Most mRNAs Are Exported from the Nucleus by a ran-Independent Mechanism
	14 Vesicular Traffic, Secretion, and Endocytosis
		14.1 Techniques for Studying the Secretory Pathway
			Transport of a Protein Through the Secretory Pathway Can Be Assayed in Live Cells
			Yeast Mutants Define Major Stages and Many components in Vesicular Transport
			Cell-Free Transport Assays Allow Dissection of Individual Steps in Vesicular Transport
		14.2 Molecular Mechanisms of Vesicle Budding and Fusion
			Assembly of a Protein Coat Drives Vesicle formation and Selection of Cargo Molecules
			A Conserved Set of GTPase Switch Proteins Controls the Assembly of Different Vesicle Coats
			Targeting Sequences on Cargo Proteins Make Specific Molecular Contacts with Coat Proteins
			Rab GTPases Control Docking of Vesicles on Target Membranes
			Paired Sets of SNARE Proteins Mediate Fusion of Vesicles with Target Membranes
			Dissociation of SNARE Complexes After Membrane Fusion Is Driven by ATP Hydrolysis
		14.3 Early Stages of the Secretory Pathway
			COPII Vesicles Mediate Transport from the ER to the Golgi
			COPI Vesicles Mediate Retrograde Transport Within the Golgi and from the Golgi to the ER
			Anterograde Transport Through the Golgi Occurs by Cisternal Maturation
		14.4 Later Stages of the Secretory Pathway
			Vesicles Coated with Clathrin and Adapter Proteins Mediate Transport from the trans-Golgi
			Dynamin Is required for Pinching Off of Clathrin-coated Vesicles
			Mannose 6-Phosphate residues Target Soluble Proteins to Lysosomes
			Study of Lysosomal Storage Diseases Revealed Key Components of the Lysosomal Sorting Pathway
			Protein Aggregation in the trans-Golgi May Function in Sorting Proteins to Regulated Secretory Vesicles
			Some Proteins Undergo Proteolytic Processing After Leaving the trans-Golgi
			Several Pathways Sort Membrane Proteins to the Apical or Basolateral Region of Polarized Cells
		14.5 Receptor-Mediated Endocytosis
			Cells Take Up Lipids from the Blood in the Form of Large, Well-Defined Lipoprotein Complexes
			Receptors for Macromolecular Ligands Contain Sorting Signals That Target Them for Endocytosis
			The Acidic pH of Late Endosomes Causes Most Receptor-Ligand Complexes to Dissociate
			The Endocytic Pathway Delivers Iron to Cells Without Dissociation of the Transferrin-Transferrin Receptor Complex in Endosomes
		14.6 Directing Membrane Proteins and Cytosolic Materials to the Lysosome
			Multivesicular Endosomes Segregate Membrane Proteins Destined for the Lysosomal Membrane from Proteins Destined for Lysosomal Degradation
			Retroviruses Bud from the Plasma Membrane by a Process Similar to formation of Multivesicular Endosomes
			The Autophagic Pathway Delivers Cytosolic Proteins or Entir Organelles to Lysosomes
	15 Signal Transduction and G Protein-Coupled Receptors
		15.1 Signal Transduction: From Extracellular Signal to Cellular Response
			Signaling Molecules Can Act Locally or at a Distance
			Receptors Bind Only a Single Type of Hormone or a Group of Closely Related Hormones
			Protein Kinases and Phosphatases Are Employed in Many Signaling Pathways
			GTP-Binding Proteins Are Frequently Used in Signal Transduction Pathways as On/Off Switches
			Intracellular “Second Messengers” Transmit Signals from Many Receptors
			Signal Transduction Pathways Can Amplify the Effects of Extracellular Signals
		15.2 Studying Cell-Surface Receptors and Signal Transduction Proteins
			The Dissociation Constant Is a Measure of the Affinity of a receptor for Its Ligand
			Binding Assays Are Used to Detect Receptors and Determine Their Affinity and Specificity for Ligands
			Near-Maximal Cellular Response to a Signaling Molecule Usually Does Not Require Activation of All Receptors
			Sensitivity of a Cell to External Signals Is Determined by the Number of Cell-Surface Receptors and Their Affinity for Ligand
			Hormone Analogs Are Widely Used as Drugs
			Receptors Can Be Purified by Affinity Chromatography Techniques
			Immunoprecipitation Assays and Affinity Techniques Can Be Used to Study the Activity of Signal Transduction Proteins
		15.3 G Protein-Coupled Receptors:Structure and Mechanism
			All G Protein–Coupled Receptors Share the Same Basic Structure
			Ligand-activated G Protein–Coupled Receptors Catalyze Exchange of GTP for GDP on the α Subunit of a Heterotrimeric G Protein
			Different G Proteins Are Activated by Different GPcrs and In Turn Regulate Different Effector Proteins
		15.4 G Protein-Coupled Receptors That Regulate Ion Channels
			Acetylcholine Receptors in the Heart Muscle Activate a G Protein That Opens K+ Channels
			Light Activates Rhodopsin in Rod Cells of the Eye
			Activation of Rhodopsin by Light Leads to Closing of cGMP-Gated Cation Channels
			Signal Amplification Makes the Rhodopsin Signal Transduction Pathway Exquisitely Sensitive
			Rapid Termination of the Rhodopsin Signal Transduction Pathway Is Essential for the Temporal Resolution of Vision
			Rod Cells Adapt to Varying Levels of Ambient Light by Intracellular Trafficking of Arrestin and Transducin
		15.5 G Protein-Coupled Receptors That Activate or Inhibit Adenylyl Cyclase
			Adenylyl Cyclase Is Stimulated and Inhibited by Different Receptor-Ligand Complexes
			Structural Studies Established How Gas-GTP Binds to and Activates Adenylyl Cyclase
			cAMP Activates Protein Kinase a by Releasing Inhibitory Subunits
			Glycogen Metabolism Is Regulated by Hormone-Induced Activation of PKA
			cAMP-Mediated Activation of PKA Produces Diverse responses in Different Cell Types
			Signal Amplification Occurs in the cAMP-PKA Pathway
			CREB links cAMP and PKA to Activation of Gene Transcription
			Anchoring Proteins Localize Effects of cAMP to Specific Regions of the Cell
			Multiple Mechanisms Suppress Signaling from the GPCR/cAMP/PKA Pathway
		15.6 G Protein-Coupled Receptors That Trigger Elevations in Cytosolic and Mitochondrial Calcium
			Calcium Concentrations in the Mitochondrial Matrix, ER, and Cytosol Can Be Measured with Targeted Fluorescent Proteins
			Activated Phospholipase C Generates Two Key Second Messengers Derived from the Membrane Lipid Phosphatidylinositol 4,5-Bisphosphate
			The Ca2+-Calmodulin Complex Mediates Many Cellular Responses to External Signals
			DAG Activates Protein Kinase C
			Integration of Ca2+ and cAMP Second Messengers Regulates Glycogenolysis
			Signal-Induced Relaxation of Vascular Smooth Muscle Is Mediated by a Ca2+-Nitric Oxide-cGMP-activated Protein Kinase G Pathway
	16 Signaling Pathways That Control Gene Expression
		16.1 Receptor Serine Kinases That Activate Smads
			TGF-β Proteins are Stored in an Inactive form in the Extracellular Matrix
			Three Separate TGF-β Receptor Proteins Participate in Binding TGF-β and Activating Signal Transduction
			Activated TGF-β Receptors Phosphorylate Smad Transcription Factors
			The Smad3/Smad4 Complex Activates Expression of Different Genes in Different Cell Types
			Negative Feedback Loops Regulate TGF-β/Smad Signaling
		16.2 Cytokine Receptors and the JAK/STAT Signaling Pathway
			Cytokines Influence the Development of Many Cell Types
			Binding of a Cytokine to Its Receptor Activates One or More Tightly Bound JaK Protein Tyrosine Kinases
			Phosphotyrosine Residues Are Binding Surfaces for Multiple Proteins with Conserved Domains
			SH2 Domains in Action: JAK Kinases Activate STAT Transcription Factors
			Multiple Mechanisms Down-Regulate Signaling from Cytokine Receptors
		16.3 Receptor Tyrosine Kinases
			Binding of Ligand Promotes Dimerization of an RTK and Leads to Activation of Its Intrinsic Tyrosine Kinase
			Homo- and Hetero-Oligomers of Epidermal Growth Factor Receptors Bind Members of the Epidermal Growth Factor Family
			Activation of the EGF Receptor Results in the Formation of an Asymmetric Active Kinase Dimer
			Multiple Mechanisms Down-Regulate Signaling from RTKs
		16.4 The Ras/MAP Kinase Pathway
			Ras, a GTPase Switch Protein, Operates Downstream of Most RTKs and Cytokine Receptors
			Genetic Studies in Drosophila Identified Key Signal-Transducing Proteins in the Ras/MaP Kinase Pathway
			Receptor Tyrosine Kinases are Linked to Ras by Adapter Proteins
			Binding of Sos to Inactive Ras Causes a Conformational Change That Triggers an Exchange of GTP for GDP
			Signals Pass from Activated Ras to a Cascade of Protein Kinases Ending with MaP Kinase
			Phosphorylation of MAP Kinase Results in a Conformational Change That Enhances Its Catalytic Activity and Promotes Its Dimerization
			MAP Kinase Regulates the Activity of Many Transcription Factors Controlling Early Response Genes
			G Protein–Coupled Receptors Transmit Signals to MaP Kinase in Yeast Mating Pathways
			Scaffold Proteins Separate Multiple MAP Kinase Pathways in Eukaryotic Cells
		16.5 Phosphoinositide Signaling Pathways
			Phospholipase cγ Is Activated by Some RTKs and Cytokine Receptors
			Recruitment of PI-3 Kinase to Activated Receptors Leads to Synthesis of Three Phosphorylated Phosphatidylinositols
			Accumulation of PI 3-Phosphates in the Plasma Membrane Leads to Activation of Several Kinases
			Activated Protein Kinase B Induces Many Cellular Responses
			The PI-3 Kinase Pathway Is Negatively Regulated by PTEN Phosphatase
		16.6 Signaling Pathways Controlled by Ubiquitinylation and Protein Degradation: Wnt, Hedgehog, and NF-κB
			Wnt Signaling Triggers Release of a Transcription Factor from a Cytosolic Protein Complex
			Concentration Gradients of Wnt Protein Are Essential for Many Steps in Development
			Hedgehog Signaling Relieves Repression of Target Genes
			Hedgehog Signaling in Vertebrates Requires Primary Cilia
			Degradation of an Inhibitor Protein Activates the NF-κB Transcription Factor
			Polyubiquitin Chains Serve as Scaffolds Linking Receptors to Downstream Proteins in the NF-κB Pathway
		16.7 Signaling Pathways Controlled by Protein Cleavage: Notch/Delta, SREBP, and Alzheimer’s Disease
			On Binding Delta, the Notch Receptor Is Cleaved, Releasing a Component Transcription Factor
			Matrix Metalloproteases Catalyze Cleavage of Many Signaling Proteins from the Cell Surface
			Inappropriate Cleavage of Amyloid Precursor Protein Can Lead to Alzheimer’s Disease
			Regulated Intramembrane Proteolysis of SREBPs Releases a Transcription Factor That Acts to Maintain Phospholipid and Cholesterol Levels
		16.8 Integration of Cellular Responses to Multiple Signaling Pathways: Insulin Action
			Insulin and Glucagon Work Together to Maintain a Stable Blood Glucose Level
			A Rise in Blood Glucose Triggers Insulin Secretion from the β Islet Cells
			In Fat and Muscle Cells, Insulin Triggers Fusion of Intracellular Vesicles Containing the GLUT4 Glucose Transporter to the Plasma Membrane
			Insulin Inhibits Glucose Synthesis and Enhances Storage of Glucose as Glycogen
			Multiple Signal Transduction Pathways Interact to Regulate Adipocyte Differentiation Through PPARγ, the Master Transcriptional Regulator
			Inflammatory Hormones Cause Derangement of Adipose Cell Function in Obesity
	17 Cell Organization and Movement I: Microfilaments
		17.1 Microfilaments and Actin Structures
			Actin Is Ancient, Abundant, and Highly Conserved
			G-Actin Monomers Assemble into Long, Helical F-Actin Polymers
			F-Actin Has Structural and Functional Polarity
		17.2 Dynamics of Actin Filaments
			Actin Polymerization In Vitro Proceeds in Three Steps
			Actin Filaments Grow Faster at (+) Ends Than at (–) Ends
			Actin Filament Treadmilling Is Accelerated by Profilin and Cofilin
			Thymosin-β4 Provides a Reservoir of Actin for Polymerization
			Capping Proteins Block Assembly and Disassembly at Actin Filament Ends
		17.3 Mechanisms of Actin Filament Assembly
			Formins Assemble Unbranched Filaments
			The Arp2/3 Complex Nucleates Branched Filament Assembly
			Intracellular Movements Can Be Powered by Actin Polymerization
			Microfilaments function in Endocytosis
			Toxins That Perturb the Pool of Actin Monomers are Useful for Studying Actin Dynamics
		17.4 Organization of Actin-Based Cellular Structures
			Cross-Linking Proteins Organize Actin Filaments into Bundles or Networks
			Adapter Proteins Link Actin Filaments to Membranes
		17.5 Myosins: Actin-Based Motor Proteins
			Myosins Have Head, Neck, and Tail Domains with Distinct Functions
			Myosins Make Up a Large Family of Mechanochemical Motor Proteins
			Conformational Changes in the Myosin Head Couple ATP Hydrolysis to Movement
			Myosin Heads Take Discrete Steps Along Actin Filaments
		17.6 Myosin-Powered Movements
			Myosin Thick Filaments and Actin Thin Filaments in Skeletal Muscle Slide Past Each Other During Contraction
			Skeletal Muscle Is Structured by Stabilizing and Scaffolding Proteins
			Contraction of Skeletal Muscle Is Regulated by Ca2+ and Actin-Binding Proteins
			Actin and Myosin II form Contractile Bundles in Nonmuscle Cells
			Myosin-Dependent Mechanisms Regulate Contraction in Smooth Muscle and Nonmuscle Cells
			Myosin V–Bound Vesicles are Carried Along Actin Filaments
		17.7 Cell Migration: Mechanism,Signaling, and Chemotaxis
			Cell Migration Coordinates Force Generation with Cell Adhesion and Membrane Recycling
			The Small GTP-Binding Proteins Cdc42, Rac, and Rho Control Actin Organization
			Cell Migration Involves the Coordinate Regulation of Cdc42, Rac, and Rho
			Migrating Cells Are Steered by Chemotactic Molecules
	18 Cell Organization and Movement II: Microtubules and Intermediate Filaments
		18.1 Microtubule Structure and Organization
			Microtubule Walls are Polarized Structures Built from αβ-Tubulin Dimers
			Microtubules are Assembled from MTOCs to Generate Diverse Configurations
		18.2 Microtubule Dynamics
			Individual Microtubules Exhibit Dynamic Instability
			Localized Assembly and “Search and Capture” Help Organize Microtubules
			Drugs Affecting Tubulin Polymerization Are Useful Experimentally and in Treatment of Diseases
		18.3 Regulation of Microtubule Structure and Dynamics
			Microtubules are Stabilized by Side-Binding Proteins
			+TIPs Regulate the Properties and Functions of the Microtubule (+) End
			Other End-Binding Proteins Regulate Microtubule Disassembly
		18.4 Kinesins and Dyneins: Microtubule-Based Motor Proteins
			Organelles in Axons Are Transported Along Microtubules in Both Directions
			Kinesin-1 Powers Anterograde Transport Of Vesicles Down axons Toward the (+) Ends of Microtubules
			The Kinesins form a Large Protein Superfamily with Diverse Functions
			Kinesin-1 Is a Highly Processive Motor
			Dynein Motors Transport Organelles Toward the (—) Ends of Microtubules
			Kinesins and Dyneins Cooperate in the Transport of Organelles Throughout the Cell Tubulin Modifications Distinguish Different Classes of Microtubules and Their Accessibility to Motors
		18.5 Cilia and Flagella: Microtubule-Based Surface Structures
			Eukaryotic Cilia and Flagella Contain Long Doublet Microtubules Bridged by Dynein Motors
			Ciliary and Flagellar Beating Are Produced by Controlled Sliding of Outer Doublet Microtubules
			Intraflagellar Transport Moves Material Up and Down Cilia and Flagella
			Primary Cilia Are Sensory Organelles on Interphase Cells
			Defects in Primary Cilia Underlie Many Diseases
		18.6 Mitosis
			Centrosomes Duplicate Early in the Cell Cycle in Preparation for Mitosis
			Mitosis can Be Divided into Six Stages
			The Mitotic Spindle Contains Three Classes of MiCrotubules
			Microtubule Dynamics Increase Dramatically in Mitosis
			Mitotic Asters Are Pushed Apart by Kinesin-5 and Oriented by Dynein
			Chromosomes Are Captured and Oriented During Prometaphase
			Duplicated Chromosomes Are Aligned by Motors and Microtubule Dynamics
			The Chromosomal Passenger Complex Regulates Microtubule Attachment at Kinetochores
			Anaphase A Moves Chromosomes to Poles by Microtubule Shortening
			Anaphase B Separates Poles by the Combined Action of Kinesins and Dynein
			Additional Mechanisms Contribute to Spindle formation
			Cytokinesis Splits the Duplicated Cell in Two
			Plant Cells Reorganize Their Microtubules and Build a New Cell Wall in Mitosis
		18.7 Intermediate Filaments
			Intermediate Filaments Are Assembled from Subunit Dimers
			Intermediate Filaments Are Dynamic
			Cytoplasmic Intermediate Filament Proteins Are Expressed in a Tissue-Specific Manner
			Lamins Line the Inner Nuclear Envelope To Provide Organization and Rigidity to the Nucleus
			Lamins Are Reversibly Disassembled by Phosphorylation During Mitosis
		18.8 Coordination and Cooperation Between Cytoskeletal Elements
			Intermediate Filament–Associated Proteins Contribute to Cellular Organization
			Microfilaments and Microtubules Cooperate to Transport Melanosomes
			Cdc42 Coordinates Microtubules and Microfilaments During Cell Migration
			Advancement of Neural Growth Cones Is Coordinated by Microfilaments and Microtubules
	19 The Eukaryotic Cell Cycle
		19.1 Overview of the Cell Cycle and Its Control
			The Cell Cycle Is an Ordered Series of Events Leading to Cell Replication
			Cyclin-Dependent Kinases Control the Eukaryotic Cell Cycle
			Several Key Principles Govern the Cell Cycle
		19.2 Model Organisms and Methods of Studying the Cell Cycle
			Budding and Fission Yeasts are Powerful Systems for Genetic Analysis of the Cell Cycle
			Frog Oocytes and Early Embryos Facilitate Biochemical Characterization of the Cell Cycle Machinery
			Fruit Flies Reveal the Interplay Between Development and the Cell Cycle
			The Study of Tissue Culture Cells Uncovers Cell Cycle Regulation in Mammals
			Researchers Use Multiple Tools to Study the Cell Cycle
		19.3 Regulation of CDK Activity
			Cyclin-Dependent Kinases Are Small Protein Kinases That Require a Regulatory Cyclin Subunit for Their Activity
			Cyclins Determine the Activity of CDKs
			Cyclin Levels Are Primarily Regulated by Protein Degradation
			CDKs Are Regulated by Activating and Inhibitory Phosphorylation
			CDK Inhibitors Control Cyclin-CDK Activity
			Genetically Engineered CDKs Led to the Discovery of CDK Functions
		19.4 Commitment to the Cell Cycle and DNA Replication
			Cells Are Irreversibly Committed to Division at a Cell Cycle Point Called START or the Restriction Point
			The E2F Transcription Factor and Its Regulator Rb Control the G1–S Phase Transition in Metazoans
			Extracellular Signals Govern Cell Cycle Entry
			Degradation of an S Phase CDK Inhibitor Triggers DNA Replication
			Replication at Each Origin Is Initiated Once and Only Once During the Cell Cycle
			Duplicated DNA Strands Become Linked During Replication
		19.5 Entry into Mitosis
			Precipitous Activation of Mitotic CDKs Initiates Mitosis
			Mitotic CDKs Promote Nuclear Envelope Breakdown
			Mitotic CDKs Promote Mitotic Spindle Formation
			Chromosome Condensation Facilitates Chromosome Segregation
		19.6 Completion of Mitosis: Chromosome Segregation and Exit from Mitosis
			Separase-Mediated Cleavage of Cohesins Initiates Chromosome Segregation
			APC/C Activates Separase Through Securin Ubiquitinylation
			Mitotic CDK Inactivation Triggers Exit from Mitosis
			Cytokinesis Creates Two Daughter Cells
		19.7 Surveillance Mechanisms in Cell Cycle Regulation
			Checkpoint Pathways Establish Dependencies and Prevent Errors in the Cell Cycle
			The Growth Checkpoint Pathway Ensures That Cells Enter the Cell Cycle Only After Sufficient Macromolecule Biosynthesis
			The DNA Damage Response System Halts Cell Cycle Progression When DNA Is Compromised
			The Spindle Assembly Checkpoint Pathway Prevents Chromosome Segregation Until Chromosomes Are Accurately Attached to the Mitotic Spindle
			The Spindle Position Checkpoint Pathway Ensures That the Nucleus Is Accurately Partitioned Between Two Daughter Cells
		19.8 Meiosis: A Special Type of Cell Division
			Extracellular and Intracellular Cues Regulate Germ Cell Formation
			Several Key Features Distinguish Meiosis from Mitosis
			Recombination and a Meiosis-Specific Cohesin Subunit Are Necessary for the Specialized Chromosome Segregation in Meiosis I
			Co-orienting Sister Kinetochores Is Critical for Meiosis I Chromosome Segregation
			DNA Replication Is Inhibited Between the Two Meiotic Divisions
Part IV Cell Growth and Differentiation
	20 Integrating Cells into Tissues
		20.1 Cell-Cell and Cell-Extracellular Matrix Adhesion: An Overview
			Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins
			The Extracellular Matrix Participates in Adhesion, Signaling, and Other Functions
			The Evolution of Multifaceted Adhesion Molecules Made Possible the Evolution of Diverse Animal Tissues
			Cell-Adhesion Molecules Mediate Mechanotransduction
		20.2 Cell-Cell and Cell-Extracellular Junctions and Their Adhesion Molecules
			Epithelial Cells Have Distinct Apical, Lateral, and Basal Surfaces
			Three Types of Junctions Mediate Many Cell-Cell and Cell-ECM Interactions
			Cadherins Mediate Cell-Cell Adhesions In Adherens Junctions and Desmosomes
			Integrins Mediate Cell-ECM Adhesions, Including Those in Epithelial-Cell Hemidesmosomes
			Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components
			Gap Junctions Composed of Connexins Allow Small Molecules to Pass Directly Between the Cytosols of Adjacent Cells
		20.3 The Extracellular Matrix I: The Basal Lamina
			The Basal Lamina Provides a Foundation For Assembly of Cells into Tissues
			Laminin, a Multi-adhesive Matrix Protein, Helps Cross-Link Components of the Basal Lamina
			Sheet-Forming Type IV Collagen Is a Major Structural Component of the Basal Lamina
			Perlecan, a Proteoglycan, Cross-Links Components of the Basal Lamina and Cell-Surface Receptors
		20.4 The Extracellular Matrix II: Connective Tissue
			Fibrillar Collagens Are the Major Fibrous Proteins in the ECM of Connective Tissues
			Fibrillar Collagen Is Secreted and Assembled into Fibrils Outside the Cell
			Type I and II Collagens Associate with Nonfibrillar Collagens to Form Diverse Structures
			Proteoglycans and Their Constituent GAGs Play Diverse Roles in the ECM
			Hyaluronan Resists Compression, Facilitates Cell Migration, and Gives Cartilage Its Gel-Like Properties
			Fibronectins Connect Cells and ECM, Influencing Cell Shape, Differentiation, and Movement
			Elastic Fibers Permit Many Tissues to Undergo Repeated Stretching and Recoiling
			Metalloproteases Remodel and Degrade the Extracellular Matrix
		20.5 Adhesive Interactions in Motile and Nonmotile Cells
			Integrins Mediate Adhesion and Relay Signals Between Cells and Their Three-Dimensional Environment
			Regulation of Integrin-Mediated Adhesion and Signaling Controls Cell Movement
			Connections Between the ECM and Cytoskeleton Are Defective in Muscular Dystrophy
			IgCAMs Mediate Cell-Cell Adhesion in Neural and Other Tissues
			Leukocyte Movement into Tissues Is Orchestrated by a Precisely Timed Sequence of Adhesive Interactions
		20.6 Plant Tissues
			The Plant Cell Wall Is a Laminate of Cellulose Fibrils in a Matrix of Glycoproteins
			Loosening of the Cell Wall Permits Plant Cell Growth
			Plasmodesmata Directly Connect the Cytosols of Adjacent Cells
			Tunneling Nanotubes Resemble Plasmodesmata and Transfer Molecules and Organelles Between Animal Cells
			Only a Few Adhesion Molecules Have Been Identified in Plants
	21 Stem Cells, Cell Asymmetry, and Cell Death
		21.1 Early Mammalian Development
			Fertilization Unifies the Genome
			Cleavage of the Mammalian Embryo Leads to the First Differentiation Events
		21.2 Embryonic Stem Cells and Induced Pluripotent Stem Cells
			The Inner Cell Mass Is the Source of ES Cells
			Multiple Factors Control the Pluripotency of ES Cells
			Animal Cloning Shows That Differentiation Can Be Reversed
			Somatic Cells Can Generate iPS Cells
			ES and iPS Cells Can Generate Functional Differentiated Human Cells
		21.3 Stem Cells and Niches in Multicellular Organisms
			Adult Planaria Contain Pluripotent Stem Cells
			Multipotent Somatic Stem Cells Give Rise to Both Stem Cells and Differentiating Cells
			Stem Cells for Different Tissues Occupy Sustaining Niches
			Germ-line Stem Cells Produce Sperm or Oocytes
			Intestinal Stem Cells Continuously Generate all the Cells of the Intestinal Epithelium
			Hematopoietic Stem Cells form all Blood Cells
			Rare Types of Cells Constitute the Niche for Hematopoietic Stem Cells
			Meristems Are Niches for Stem Cells in Plants
			A Negative Feedback Loop Maintains the Size of the Shoot Apical Stem-Cell Population
			The Root Meristem Resembles the Shoot Meristem in Structure and Function
		21.4 Mechanisms of Cell Polarity and Asymmetric Cell Division
			The Intrinsic Polarity Program Depends on a Positive Feedback Loop Involving Cdc42
			Cell Polarization Before Cell Division Follows a Common Hierarchy of Steps
			Polarized Membrane Traffic Allows Yeast to Grow Asymmetrically During Mating
			The Par Proteins Direct Cell Asymmetry in the Nematode Embryo
			The Par Proteins and Other Polarity Complexes Are Involved in Epithelial-Cell Polarity
			The Planar Cell Polarity Pathway Orients Cells Within an Epithelium
			The Par Proteins Are Involved in Asymmetric Division of Stem Cells
		21.5 Cell Death and Its Regulation
			Most Programmed Cell Death Occurs Through Apoptosis
			Evolutionarily Conserved Proteins Participate in the Apoptotic Pathway
			Caspases Amplify the Initial Apoptotic Signal and Destroy Key Cellular Proteins
			Neurotrophins Promote Survival of Neurons
			Mitochondria Play a Central Role in Regulation of Apoptosis in Vertebrate Cells
			The Pro-Apoptotic Proteins Bax and Bak form Pores and Holes in the Outer Mitochondrial Membrane
			Release of Cytochrome c and SMAC/DIABLO Proteins from Mitochondria Leads to Formation of the Apoptosome and Caspase Activation
			Trophic Factors Induce Inactivation of Bad, a Pro-Apoptotic BH3-Only Protein
			Vertebrate apoptosis Is Regulated by BH3-Only Pro-Apoptotic Proteins That Are Activated by Environmental Stresses
			Two Types of Cell Murder Are Triggered by Tumor Necrosis Factor, Fas Ligand, and Related Death Signals
	22 Cells of the Nervous System
		22.1 Neurons and Glia: Building Blocks of the Nervous System
			Information Flows Through Neurons from Dendrites to Axons
			Information Moves Along Axons as Pulses of Ion Flow Called Action Potentials
			Information Flows Between Neurons Via Synapses
			The Nervous System Uses Signaling Circuits Composed of Multiple Neurons
			Glial Cells form Myelin Sheaths and Support Neurons
			Neural Stem Cells form Nerve and Glial Cells in the Central Nervous System
		22.2 Voltage-Gated Ion Channels and the Propagation of Action Potentials
			The Magnitude of the Action Potential Is Close to ENa and Is Caused by Na+ Influx Through Open Na+ Channels
			Sequential Opening and Closing of Voltage-Gated Na+ and K+ Channels Generate Action Potentials
			Action Potentials Are Propagated Unidirectionally Without Diminution
			Nerve Cells Can Conduct Many Action Potentials in the Absence of ATP
			All Voltage-Gated Ion Channels Have Similar Structures
			Voltage-Sensing S4 α Helices Move in Response to Membrane Depolarization
			Movement of the Channel-Inactivating Segment into the Open Pore Blocks Ion Flow
			Myelination Increases the Velocity of Impulse Conduction
			Action Potentials “Jump” from Node to Node in Myelinated Axons
			Two Types of Glia Produce Myelin Sheaths
			Light-Activated Ion Channels and Optogenetics
		22.3 Communication at Synapses
			Formation of Synapses Requires Assembly of Presynaptic and Postsynaptic Structures
			Neurotransmitters Are Transported into Synaptic Vesicles by H+-Linked Antiport Proteins
			Three Pools of Synaptic Vesicles Loaded With Neuro Transmitter Are Present in the Presynaptic Terminal
			Influx of Ca2+ Triggers Release of Neurotransmitters
			A calcium-Binding Protein Regulates Fusion of Synaptic Vesicles with the Plasma Membrane
			Fly Mutants Lacking Dynamin Cannot Recycle Synaptic Vesicles
			Signaling at Synapses Is Terminated by Degradation or Reuptake of Neurotransmitters
			Opening of Acetylcholine-Gated Cation Channels Leads to Muscle Contraction
			All Five Subunits in the Nicotinic Acetylcholine Receptor Contribute to the Ion Channel
			Nerve Cells Integrate Many Inputs to Make an All-or-None Decision to Generate an Action Potential
			Gap Junctions Allow Direct Communication Between Neurons and Between Glia
		22.4 Sensing the Environment: Touch, Pain, Taste, and Smell1
			Mechanoreceptors Are Gated Cation Channels
			Pain Receptors Are Also Gated Cation Channels
			Five Primary Tastes Are Sensed by Subsets of Cells in Each Taste Bud
			A Plethora of Receptors Detect Odors
			Each Olfactory Receptor Neuron Expresses a Single Type of Odorant Receptor
		22.5 Forming and Storing Memories1
			Memories Are Formed by Changing the Number or Strength of Synapses Between Neurons
			The Hippocampus Is Required for Memory Formation
			Multiple Molecular Mechanisms Contribute to Synaptic Plasticity
			Formation of Long-Term Memories Requires Gene Expression
	23 Immunology
		23.1 Overview of Host Defenses
			Pathogens Enter the Body Through Different Routes and Replicate at Different Sites
			Leukocytes circulate Throughout the Body and Take Up Residence in Tissues and Lymph Nodes
			Mechanical and Chemical Boundaries form a First Layer of Defense Against Pathogens
			Innate Immunity Provides a Second Line of Defense
			Inflammation Is a Complex Response to Injury That Encompasses Both Innate and Adaptive Immunity
			Adaptive Immunity, the Third Line of Defense, Exhibits Specificity
		23.2 Immunoglobulins: Structureand Function
			Immunoglobulins Have a Conserved Structure Consisting of Heavy and Light Chains
			Multiple Immunoglobulin Isotypes Exist, Each with Different Functions
			Each Naive B Cell Produces a Unique Immunoglobulin
			Immunoglobulin Domains Have a Characteristic Fold Composed of Two β Sheets Stabilized by a Disulfide Bond
			An Immunoglobulin’s Constant Region Determines Its Functional Properties
		23.3 Generation of Antibody Diversityand B-Cell Development
			A functional Light-Chain Gene Requires Assembly of V and J Gene Segments
			Rearrangement of the Heavy-Chain Locus Involves V, D, and J Gene Segments
			Somatic Hypermutation Allows the Generation and Selection of Antibodies with Improved Affinities
			B-cell Development Requires Input from a Pre-B-cell Receptor
			During an Adaptive Response, B Cells Switch from Making Membrane-Bound Ig to Making Secreted Ig
			B Cells Can Switch the Isotype of Immunoglobulin They Make
		23.4 The MHC and Antigen Presentation
			The MHc Determines the Ability of Two Unrelated Individuals of the Same Species to Accept or Reject Grafts
			The Killing Activity of Cytotoxic T Cells Is Antigen Specific and MHC Restricted
			T Cells with Different Functional Properties Are Guided by Two Distinct Classes of MHC Molecules
			MHC Molecules Bind Peptide Antigens and Interact with the T-Cell Receptor
			Antigen Presentation Is the Process by Which Protein Fragments Are Complexed with MHC Products and Posted to the Cell Surface
			The Class I MHC Pathway Presents Cytosolic Antigens
			The Class II MHC Pathway Presents Antigens Delivered to the Endocytic Pathway
		23.5 T Cells, T-Cell Receptors, and T-Cell Development
			The Structure of the T-Cell Receptor Resembles the F(ab) Portion of an Immunoglobulin
			TCR Genes Are Rearranged in a Manner Similar to Immunoglobulin Genes
			Many of the Variable Residues of TCRs Are Encoded in the Junctions Between V, D, and J Gene Segments
			Signaling via Antigen-Specific Receptors Triggers Proliferation and Differentiation of T and B Cells
			T Cells Capable of Recognizing MHC Molecules Develop Through a Process of Positive and Negative Selection
			T Cells Commit to the CD4 or CD8 Lineage in the Thymus
			T Cells Require Two Types of Signals for Full Activation
			Cytotoxic T Cells Carry the CD8 Co-Receptor and are Specialized for Killing
			T Cells Produce an Array of Cytokines That Provide Signals to Other Immune-System Cells
			Helper T Cells Are Divided into Distinct Subsets Based on Their Cytokine Production and Expression of Surface Markers
			Leukocytes Move in Response to Chemotactic Cues Provided by Chemokines
		23.6 Collaboration of Immune-System Cells in the Adaptive Response
			Toll-Like Receptors Perceive a Variety of Pathogen-Derived Macromolecular Patterns
			Engagement of Toll-Like Receptors Leads to Activation of Antigen-Presenting Cells
			Production of High-Affinity Antibodies Requires Collaboration Between B and T Cells
			Vaccines Elicit Protective Immunity Against a Variety of Pathogens
			The Immune System Defends Against Cancer
	24 Cancer
		24.1 How Tumor Cells Differ from Normal Cells
			The Genetic Makeup of Most Cancer Cells Is Dramatically Altered
			Cellular Housekeeping Functions Are Fundamentally Altered in Cancer Cells
			Uncontrolled Proliferation Is a Universal Trait of Cancer
			Cancer Cells Escape the Confines of Tissues
			Tumors Are Heterogeneous Organs That Are Sculpted by Their Environment
			Tumor Growth Requires Formation of New Blood Vessels
			Invasion and Metastasis Are Late Stages of Tumorigenesis
		24.2 The Origins and Developmentof Cancer
			Carcinogens Induce Cancer by Damaging DNA
			Some Carcinogens Have Been Linked to Specific Cancers
			The Multi-Hit Model Can Explain the Progress of Cancer
			Successive Oncogenic Mutations Can Be Traced in Colon Cancers
			Cancer Development Can Be Studied in Cultured Cells and in Animal Models
		24.3 The Genetic Basis of Cancer
			Gain-of-Function Mutations Convert Proto-oncogenes into Oncogenes
			Cancer-Causing Viruses Contain Oncogenes or Activate Cellular Proto-Oncogenes
			Loss-of-Function Mutations in Tumor-Suppressor Genes Are Oncogenic
			Inherited Mutations in Tumor-Suppressor Genes Increase Cancer Risk
			Epigenetic Changes Can Contribute to Tumorigenesis
			Micro-RNAs Can Promote and Inhibit Tumorigenesis
			Researchers Are Identifying Drivers of Tumorigenesis
			Molecular Cell Biology Is Changing How Cancer Is Diagnosed and Treated
		24.4 Misregulation of Cell Growthand Death Pathways in Cancer
			Oncogenic Receptors Can Promote Proliferation in the Absence of External Growth Factors
			Many Oncogenes Encode Constitutively Active Signal-Transducing Proteins
			Inappropriate Production of Nuclear Transcription Factors Can Induce Transformation
			Aberrations in SIgnaling Pathways That Control Development Are Associated With Many Cancers
			Genes That Regulate Apoptosis Can Function as Proto-Oncogenes or Tumor-Suppressor Genes
		24.5 Deregulation of the Cell Cycle and Genome Maintenance Pathways in Cancer
			Mutations That Promote Unregulated Passage from G1 to S Phase Are Oncogenic
			Loss of p53 Abolishes the DNA Damage Checkpoint
			Loss of DNA-Repair Systems Can Lead to Cancer
Back Matter
	Glossary
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