Origin and Functional Evolution of the Cdc48/p97/VCP AAA + Protein Unfolding and Remodeling Machine. Issue 9 (8th May 2016)

• Record Type: Journal Article
• Authors: Barthelme, Dominik; Sauer, Robert T.
• Is Part Of: Journal of molecular biology. Volume 428:Issue 9:Part B(2016:May 08)
• Page Start: 1861
• Page End: 1869
• Publication Date: 2016-05-08
• Subjects: AAA + machine -- protein remodeling -- human disease; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2015.11.015
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: The AAA + Cdc48 ATPase (alias p97 or VCP) is a key player in multiple ubiquitin-dependent cell signaling, degradation, and quality control pathways. Central to these broad biological functions is the ability of Cdc48 to interact with a large number of adaptor proteins and to remodel macromolecular proteins and their complexes. Different models have been proposed to explain how Cdc48 might couple ATP hydrolysis to forcible unfolding, dissociation, or remodeling of cellular clients. In this review, we provide an overview of possible mechanisms for substrate unfolding/remodeling by this conserved and essential AAA + protein machine and their adaption and possible biological function throughout evolution. Graphical abstract: Highlights: Eukaryotic Cdc48 plays essential roles in many ubiquitin-dependent cellular processes. A large variety of adaptor proteins regulate Cdc48's diverse biological functions. Archaeal Cdc48 functions with the 20S proteasome in ATP-dependent protein degradation. Mechanistic models for client protein unfolding and remodeling by Cdc48 are discussed.