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. 2010 Sep 2;1(7):753-763.
doi: 10.1177/1947601910381381.

p97-containing complexes in proliferation control and cancer: emerging culprits or guilt by association?

Affiliations

p97-containing complexes in proliferation control and cancer: emerging culprits or guilt by association?

Dale S Haines. Genes Cancer. .

Abstract

p97 (also called VCP in metazoans and CDC48 in yeast) is a highly conserved, abundant and essential type II ATPase that functions in numerous ubiquitin signaling dependent processes. p97/Cd48 activities require a growing number of adaptor or accessory proteins that promote interactions with ubiquitinated proteins. p97 has human disease relevance as it is mutated in familial cases of inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia (IBMPFD). There is also increasing evidence suggesting that p97 and/or some of its adaptors play a role in cancer. This review will summarize our existing knowledge of the biochemical, molecular and cellular activities of p97-containing complexes, with an ending focus on their potential role in malignancy.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Structure and function of p97. The modular structure of the enzyme is depicted (A) as well as where adaptors bind the ATPase. Models showing substrate movement and arginine collar–mediated denaturation (B) and remodeling by the propeller-like motion of p47 (colored in blue with functional domains UBX, SEP, and UBA noted) (C). (B and C) Cartoons show an overhead picture of p97.
Figure 2.
Figure 2.
p97 participates in various protein degradation pathways. The role of p97 and adaptors in ubiquitin signal–dependent degradation of natively folded cytosolic proteins, misfolded ER-localized proteins, and aggregate-prone cytosolic proteins.
Figure 3.
Figure 3.
p97 in malignancy. Potential functional roles of p97 and adaptors in cancer cells are depicted. An upward arrow designates how deregulation of the regulated process by overexpression may promote the proliferation or survival of cancer cells, while a downward arrow designates how underexpression may facilitate malignancy.

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