Protein Degradation Volume 2 discusses the mechanism and cellular functions of targeted protein breakdown via the ubiquitin pathway.

Features:

• Compiles information on the proteasome-mediated degradation steps of the ubiquitin pathway
• Includes latest results on novel members of the ubiquitin superfamily and their role in cellular regulation

Contents

Molecular Chaperones and the Ubiquitin–Proteasome System

• A Biomedical Perspective
• Molecular Chaperones: Mode of Action and Cellular Functions
• Chaperones: Central Players During Protein Quality Control
• Chaperones and Protein Degradation
• The CHIP Ubiquitin Ligase: A Link Between Folding and Degradation Systems
• Other Proteins That May Influence the Balance Between Chaperoneassisted Folding and Degradation

Molecular Dissection of Autophagy in the Yeast Saccharomyces cerevisiae

• Vacuoles as a Lytic Compartment in Yeast
• Discovery of Autophagy in Yeast
• Genetic Dissection of Autophagy
• Characterization of Autophagy-defective Mutants
• Cloning of ATG Genes
• Further Genes Required for Autophagy
• Selectivity of Proteins Degraded
• Induction of Autophagy
• Membrane Dynamics During Autophagy
• Monitoring Methods of Autophagy in the Yeast S. cerevisiae
• Function of Atg Proteins
• Site of Atg Protein Functioning: The Pre-autophagosomal Structure
• Atg Proteins in Higher Eukaryotes
• Atg Proteins as Markers for Autophagy in Mammalian Cells
• Physiological Role of Autophagy in Multicellular Organisms

Dissecting Intracellular Proteolysis Using Small Molecule Inhibitors and Molecular Probes

• The Proteasome as an Essential Component of Intracellular Proteolysis
• Proteasome Structure, Function, and Localization
• Proteasome Inhibitors as Tools to Study Proteasome Function
• Assessing the Biological Role of the Proteasome With Inhibitors and Probes
• Proteasome-associated Components: The Role of N-glycanase
• A Link Between Proteasomal Proteolysis and Deubiquitination

MEKK1: Dual Function as a Protein Kinase and a Ubiquitin Protein Ligase

• Types of Protein Kinases
• Functions of Protein Kinases

Proteasome Activators

• 11S Activators: Sequence and Structure
• PA26–Proteasome Complex Structures
• Biological Roles of 11S Activators
• PA200/Blm10p

The Proteasome Portal and Regulation of Proteolysis

• The Importance of Channel Gating
• A Porthole into the Proteasome
• Facilitating Traffic Through the Gated Channel

Ubiquity and Diversity of the Proteasome System

• Catalytic Machine
• Regulatory Factors
• Proteasome Assembly

Proteasome-Interacting Proteins

• Regulators of the Holoenzyme and Chaperones Involved in Assembly of the Proteasome
• Enzymes Controlling Ubiquitination and Deubiquitination
• Shuttling Proteins: Rpn10/Pus1 and UBA-UBL Proteins
• Other UBL-Containing Proteins
• VCP/p97/cdc48
• Proteasome Interactions with Transcription, Translation and DNA Repair

Structural Studies of Large, Self-compartmentalizing Proteases

• Self-compartmentalization: An Effective Way to Control Proteolysis
• ATP-dependent Proteases: The Initial Steps in the Proteolytic Pathway
• Beyond the Proteasome: ATP-independent Processing of Oligopeptides Released by the Proteasome

What the Archaeal PAN–Proteasome Complex and Bacterial ATP-dependent Proteases Can Teach Us About the 26S Proteasome

• Archaeal 20S Proteasomes
• PAN the Archaeal Homologue of the 19S Complex
• VAT, a Potential Regulator of Proteasome Function
• The Use of PAN to Understand the Energy Requirement for Proteolysis
• Direction of Substrate Translocation
• Degradation of Polyglutamine-containing Proteins
• Eubacterial ATP-dependent Proteases
• How AAA ATPases Use ATP to Catalyze Proteolysis

Biochemical Functions of Ubiquitin and Ubiquitin-like Protein Conjugation

• Ubls: A Typical Modification Cycle by an Atypical Set of Modifiers
• Origins of the Ubiquitin System
• Ubiquitin-binding Domains and Ubiquitin Receptors in the Proteasome Pathway
• Ubiquitin-binding Domains and Membrane Protein Trafficking
• Sumoylation and SUMO-binding Motifs
• General Biochemical Functions of Protein–Protein Conjugation

Index

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