» Articles » PMID: 21103003

P97-containing Complexes in Proliferation Control and Cancer: Emerging Culprits or Guilt by Association?

Overview
Journal Genes Cancer
Specialty Oncology
Date 2010 Nov 25
PMID 21103003
Citations 20
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

UBXN7 cofactor of CRL3 and CRL2 ubiquitin ligase complexes mediates reciprocal regulation of NRF2 and HIF-1α proteins.

Di Gregorio J, Cilenti L, Ambivero C, Andl T, Liao R, Zervos A Biochim Biophys Acta Mol Cell Res. 2021; 1868(4):118963.

PMID: 33444648 PMC: 7882025. DOI: 10.1016/j.bbamcr.2021.118963.


A novel function of AAA-ATPase p97/VCP in the regulation of cell motility.

Khong Z, Lai S, Koh C, Geifman-Shochat S, Li H Oncotarget. 2020; 11(1):74-85.

PMID: 32002125 PMC: 6967774. DOI: 10.18632/oncotarget.27419.


Cooperative subunit dynamics modulate p97 function.

Huang R, Ripstein Z, Rubinstein J, Kay L Proc Natl Acad Sci U S A. 2018; 116(1):158-167.

PMID: 30584095 PMC: 6320498. DOI: 10.1073/pnas.1815495116.


Proteomic profiling of VCP substrates links VCP to K6-linked ubiquitylation and c-Myc function.

Heidelberger J, Voigt A, Borisova M, Petrosino G, Ruf S, Wagner S EMBO Rep. 2018; 19(4).

PMID: 29467282 PMC: 5891417. DOI: 10.15252/embr.201744754.


Quantitative interaction mapping reveals an extended UBX domain in ASPL that disrupts functional p97 hexamers.

Arumughan A, Roske Y, Barth C, Lleras Forero L, Bravo-Rodriguez K, Redel A Nat Commun. 2016; 7:13047.

PMID: 27762274 PMC: 5080433. DOI: 10.1038/ncomms13047.


References
1.
Chin L, Olzmann J, Li L . Parkin-mediated ubiquitin signalling in aggresome formation and autophagy. Biochem Soc Trans. 2010; 38(Pt 1):144-9. PMC: 2846638. DOI: 10.1042/BST0380144. View

2.
Ju J, Miller S, Hanson P, Weihl C . Impaired protein aggregate handling and clearance underlie the pathogenesis of p97/VCP-associated disease. J Biol Chem. 2008; 283(44):30289-99. PMC: 2573070. DOI: 10.1074/jbc.M805517200. View

3.
Wang Y, Satoh A, Warren G, Meyer H, Wang Y . VCIP135 acts as a deubiquitinating enzyme during p97-p47-mediated reassembly of mitotic Golgi fragments. J Cell Biol. 2004; 164(7):973-8. PMC: 2172062. DOI: 10.1083/jcb.200401010. View

4.
Boyault C, Zhang Y, Fritah S, Caron C, Gilquin B, Kwon S . HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregates. Genes Dev. 2007; 21(17):2172-81. PMC: 1950856. DOI: 10.1101/gad.436407. View

5.
Chen Z, Sun L . Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell. 2009; 33(3):275-86. DOI: 10.1016/j.molcel.2009.01.014. View