Protein Modificomics: From Modifications to Clinical Perspectives

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PROTEIN
MODIFICOMICS
From Modifications to
Clinical Perspectives
Copyright
Contributors
Preface
1
Posttranslational Modifications of Proteins and Their Role in Biological Processes and Associated Diseases
	Introduction
	Major Posttranslational Modifications
		Acetylation
		Glycosylation and Glycation
		Hydroxylation
		Phosphorylation
		Ubiquitination
		Methylation
		Amidation
		Palmitoylation
		Myristoylation
		Prenylation
		Proteolytic Cleavage
	Functions of Posttranslational Modifications
		Role of PTM in Apoptosis and Cancer
			Regulation of Apoptosis by Posttranslational Modifications of Caspases
			Role in Cancer
		Role of PTM in Signaling
	Diseases Associated With Posttranslational Modifications
		Relation Between Mutated Posttranslational Modification Sites and Diseases
		Acetylation and Related Diseases
		Glycosylation and Related Diseases
		PTM of Proteins During Intermittent Hypoxia
	Role of Posttranslational Modifications in Protein-Protein Interaction
	Role of PTMs in Replication
		Ubiquitinylation by Unperturbed DNA Replication
		PTMs of Replication Protein A
	Role of PTMs in Transcription
		Regulation of Activity of Transcription Factor by PTMs
	Role of PTMs in Translation
	Chemical and Functional Aspects of Protein PTMs
	Role of PTMs in Histone Modification
	Conclusion and Future Prospectus
	References
	Further Reading
2
Clinical Perspective of Posttranslational Modifications
	Introduction
	Glycosylation
		Congenital Diseases
			Congenital Disorders of Glycosylation (CDGs)
			Congenital Muscular Dystrophies (CMDs)
		Neurodegenerative Diseases
		Cancer
	Acetylation
	Phosphorylation
	Carbonylation
	Methylation
	Hydroxylation
	Nitration
	Sulfation
	Palmitoylation
	Conclusion and Future Perspective
	References
3
Phosphorylation and Acetylation of Proteins as Posttranslational Modification: Implications in Human Health and Associated ...
	Introduction
	Phosphorylation
		Heat Shock Protein (Hsp27)
		KRAS
		NF-κB and IκB
		Cytochrome c (Cyt-c)
		Epidermal Growth Factor Receptor
		P53
		Eukaryotic Translation Initiation Factor 2α (elf2α)
		Tau Protein
		Insulin Resistant Substrate Protein (IRS-1)
	Protein Acetylation
		Histone Acetylation
			Signal Transducer and Activator of Transcription (STAT) Protein
			Interferon Regulatory Factor (IRF)
			Hsp 90
			Pyruvate Kinase
			Huntingtin Protein (Htt Protein)
	Conclusion and Future Prospects
	References
4
Protein Modifications and Lifestyle Disorders
	Introduction
	Deregulated Adipocyte Proteome in Obesity
	Proteostasis in Diabetes
	Protein Modification in Cardiovascular Diseases
	Modified Proteome in Rheumatoid Arthritis
	Conclusion and Future Aspects
	References
	Further Reading
5
Ubiquitin Mediated Posttranslational Modification of Proteins Involved in Various Signaling Diseases
	Introduction
	Ubiquitination in Inflammatory Pathways
	Implications of UPS in Cancer
		E3 Ubiquitin Ligases in Development of Cancer
			p53-Associated E3 Ligases
				Mdm2
				E6-AP
				ARF-BP1
				COP1
				Pirh2
			Other E3 Ubiquitin Ligases Involved in Cancer Development
				SKP1-Cullin 1-F-Box Protein (SCF) E3 Ligases
				BRCA1 /BARD1 as an E3 Ubiquitin Ligase
				Von Hippel-Lindau (VHL) Tumor Suppressor Gene
				Nedd4-Like E3 Ligases
		Role of Deubiquitinating Enzymes (DUBs) in Cancer
			Herpes Associated Ubiquitin Specific Protease (HAUSP) or USP7
			Usp28
			USP9x
			USP2a
			A20
			CYLD
	E3 Ligases in Diabetic Retinopathy (DR)
	Implications of UPS in Neurodegenerative Diseases
		Alzheimer's Disease
		Parkinson's Disease (PD)
		Huntington's Disease
		Amyotrophic Lateral Sclerosis (ALS)
		Angelman Syndrome
	Implications of UPS in Renal Disorders
		Liddle Syndrome
		Ischemic Acute Renal Failure
	Conclusion and Future Perspectives
	References
6
Role of Glycosylation in Modulating Therapeutic Efficiency of Protein Pharmaceuticals
	Introduction
	Challenges Associated With Protein Pharmaceuticals
		Physical Instability
		Aggregation
		Solubility Issue
		Chemical Degradation
		Degradation by Proteases
	Protein Glycosylation and Its Pharmacological Significance
	Modulation of Therapeutically Important Properties of Proteins by Glycoengineering
		Physical and Chemical Properties
		Aggregation
		Half-Life Extension
		Immunogenicity
		Protein Drug Delivery
		Diagnostic Therapeutics
	Conclusion and Future Direction
	References
7
Posttranslational Modification of Heterologous Human Therapeutics in Plant Host Expression Systems
	Introduction
	N-Glycosylation as a Major Posttranslational Modification
	Factors Affecting the Natural Glycosylation of Plant-Farmed Human Pharmaceuticals
		Subcellular Compartmentalization
		The Protein Structures
		Environmental and Physiological Factors
	Plant Cell Culture Versus Whole Plant Cultivation for Biopharmaceutical Production
	Developing Humanized and Improved Glycoproteins
	Glycoengineering: Concept of ``Biobetters´´ and ``Biosimilars´´
	Success Stories
	Ebola Virus Infection
	Gaucher's Disease
	Monoclonal Antibodies
	Vaccines
	Benefits of Plant Expression System
	Limitations of Plant Expression System
	Conclusion and Future Prospects
	References
8
Protein Modification in Plants in Response to Abiotic Stress
	Introduction
	Abiotic Stress in Plants
	Types of Abiotic Stress in Plants and the Proteins Involved Therein
		Drought Stress and Associated Proteins
		Cold Stress and Cold-Induced Proteins
		Salinity Stress and the Proteins Induced Thereby
		Heat Stress and Heat Shock Induced Proteins
		Heavy Metal Stress and the Proteins Involved
		Flooding Stress in Plants
	Protein Modification in Plants in Response to Stress
		Phosphorylation
		Acetylation
		Glycosylation
		Succinylation
		Ubiquitination
		S-Nitrosylation and Tyrosine Nitration
	Conclusion and Future Perspective
	References
	Further Reading
9
Posttranslational Modifications Associated With Cancer and Their Therapeutic Implications
	Introduction
	Posttranslational Modifications That Regulate the Mdm2-p53 Interaction
	Modification of Retionblastoma Tumor Suppressor Protein (pRB) and Its Association to Cell Cycle Progression
	Regulation of NF-κB by Various Posttranslational Modifications
	Regulation of Gene Expression Via Histone and Histone Deacetylase Modifications
	Deregulation of Tyrosine Kinase by Posttranslational Modifications
	Posttranslational Modifications in Ras/Raf/MEK/ERK in MAPK Pathway
	Modification of Signal Transducers and Activators of Transcription
	Phosphorylation of Cyclin-Dependent Kinases and Their Therapeutic Implications
	Posttranslational Modification in Cadherins
	Prenylation and G-Protein Coupled Receptors
	Summary and Future Perspectives
	References
10
Nonenzymatic Posttranslational Protein Modifications: Mechanism and Associated Disease Pathologies
	Introduction
	Carbamylation
		Mechanism
		Contribution to Diseases
			Chronic Kidney Disease
			Cardiovascular Disease
			Sickle Cell Disease and Cataracts
			Rheumatoid Arthritis
			Other Pathologies
	Carbonylation
		Mechanism
		Contribution in Diseases
			Alzheimer's Disease
			Chronic Lung Disease
			Disuse Muscle Atrophy
			Chronic Renal Failure
			Diabetes
	N-Homocysteinylation
		Mechanism
		Contribution to Diseases
			Tau Homocysteinylation
			Prion Protein
	S-Nitrosylation
		Mechanism
		Contribution to Diseases
			Neurodegeneration
			Cancer
	Glycation
		Mechanism
		Contribution to Diseases
			Diabetic Complications
				Retinopathy
				Cardiomyopathy
			Alzheimer's Disease
			Parkinson's Disease
	Summary
	Acknowledgment
	References
11
Protein Covalent Modification by Homocysteine: Consequences and Clinical Implications
	Introduction
	Homocysteine and Protein Homocysteinylation
	Protein S-Homocysteinylation
	Protein N-Homocysteinylation
		HTL Induced Covalent Modification Leads to Molten Globule State Formation
		N-Homocysteinylation-Induced Structural Alteration is Protein Dependent
		Reactivity Toward HTL-Induced Covalent Modification
		N-Homocysteinylation Induces Aggregate or Amyloid Formation
		Functional Consequences of N-Homocysteinylation
		Effect on the Reservoir Proteins
	Homocystinuria/Hyperhomocysteinemia: Condition Persisting for Protein Modifications
	Clinical Complications Associated With Elevated Hcy
		Homocystinuria is Associated With Various Birth Defects
		Increased Hcy and Megaloblastic Anemia
		Hyperhomocysteinemia Results in Cardiovascular Complications
		Hcy and Renal Failure
		Hcy and Bone Deformation
		Elevated Hcy Levels are Associated With Cancer
			Low Plasma Folate Predisposes to Cancer
			Cancer Patients Have High Plasma Hcy
			Cancer Patients Develop Thromboembolism Due to Hcy Toxicity
		Elevated Hcy Levels and Its Association With NDs
	Conclusions and Future Prospects
	References
	Further Reading
12
Posttranslational Modifications in Algae: Role in Stress Response and Biopharmaceutical Production
	Introduction
	Posttranslational Modifications in Algae With Respect to Stress Response
		Phosphorylation and Stress
		Ubiquitination and Stress
		SUMOylation and Stress
		Psychrophilic Microalga and PTM
	Posttranslational Modification of Therapeutic Proteins in Microalgae
		Algae as an Emerging Recombinant Protein Production Platform
		Posttranslational Modification in Perspective of Expression of Therapeutic Proteins in Algae
		Posttranslational Modification in Algae Derived Therapeutic Proteins
	Conclusion and Future Prospects
	References
	Further Reading
13
Protein Glycosylation: An Important Tool for Diagnosis or Early Detection of Diseases
	Introduction
	Protein Posttranslational Modifications and Quest for Clinical Biomarkers
	Protein Glycosylation and Related Disorders
		Congenital Disorders of Glycosylation
		Age Related Glycosylation Disorders
		Glycosylation in Cancer: Diagnostic and Therapeutic Implications
	Technological Approaches in Analysis of Protein Glycosylation
		Preparation and Enrichment of Glycoproteins
		Mass Spectrometry Techniques for Glycoproteome Analysis
	Conclusions and Future Prospectus
	References
	Further Reading
Index
	A
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	R
	S
	T
	U
	Z
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