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Updated: Aug 9, 2025
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Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
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Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine.
Hemmo Meyer1, Johannes van den Boom1
1Center of Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen, Germany.
Frontiers in Molecular Biosciences
|February 24, 2023
Summary
The AAA+ ATPase p97 (also called VCP or Cdc48) protein unfolding machine uses two adapter systems to target diverse cellular clients for degradation or regulation. This process involves ubiquitin-dependent or -independent pathways converging on p97 for unfolding.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- AAA+ ATPase p97 (VCP/Cdc48) is a crucial protein machine involved in numerous cellular processes.
- It regulates cell homeostasis, proliferation, and signaling by interacting with hundreds of client proteins.
Purpose of the Study:
- To review recent advances in understanding how client proteins are targeted to the p97 machine.
- To elucidate the mechanisms of client degradation and regulation mediated by p97.
Main Methods:
- Review of recent scientific literature on p97 function and regulation.
- Analysis of the roles of alternative adapter proteins in p97-mediated processes.
Main Results:
- Two main adapter systems target clients to p97: Ufd1-Npl4 (ubiquitin-dependent) and SEP-domain adapters like p37 (ubiquitin-independent).
- Both pathways converge on p97's central channel for client unfolding, membrane extraction, and complex disassembly.
Conclusions:
- p97 utilizes distinct adapter systems for diverse client targeting, highlighting its versatility.
- The conserved mechanism of peptide threading through the p97 pore drives essential cellular functions.
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