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Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system

Nature Cell Biology volume 14, pages 117–123 (2012)Cite this article

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Abstract

The ATP-driven chaperone valosin-containing protein (VCP)/p97 governs critical steps in ubiquitin-dependent protein quality control and intracellular signalling pathways. It cooperates with diverse partner proteins to help process ubiquitin-labelled proteins for recycling or degradation by the proteasome in many cellular contexts. Recent studies have uncovered unexpected cellular functions for p97 in autophagy, endosomal sorting and regulating protein degradation at the outer mitochondrial membrane, and elucidated a role for p97 in key chromatin-associated processes. These findings extend the functional relevance of p97 to lysosomal degradation and reveal a surprising dual role in protecting cells from protein stress and ensuring genome stability during proliferation.

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Figure 1: The hexameric AAA+ protein VCP/p97 and its cofactors.
Figure 2: Models for p97 activity in the ubiquitin system.
Figure 3: Emerging cellular roles of p97 in interphase.

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Acknowledgements

We thank M. Ehrmann, P. Freemont, C. C. Weihl and V. Panse for critical reading. H. M. is supported by the DFG priority program SPP1365/2. We apologize to many colleagues whose work was not cited due to space limitations.

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  1. Hemmo Meyer, Monika Bug and Sebastian Bremer are at the Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, 45117 Essen, Germany,

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Meyer, H., Bug, M. & Bremer, S. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol 14, 117–123 (2012). https://doi.org/10.1038/ncb2407

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