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Review
. 2014 Sep 15;127(Pt 18):3877-83.
doi: 10.1242/jcs.093831. Epub 2014 Aug 21.

The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis

Hemmo Meyer  1 , Conrad C Weihl  2
Affiliations
Review

The VCP/p97 system at a glance: connecting cellular function to disease pathogenesis

Hemmo Meyer et al. J Cell Sci. .

Abstract

The ATPase valosin-containing protein (VCP)/p97 has emerged as a central and important element of the ubiquitin system. Together with a network of cofactors, it regulates an ever-expanding range of processes that stretch into almost every aspect of cellular physiology. Its main role in proteostasis and key functions in signaling pathways are of relevance to degenerative diseases and genomic stability. In this Cell Science at a Glance and the accompanying poster, we give a brief overview of this complex system. In addition, we discuss the pathogenic basis for VCP/p97-associated diseases and then highlight in more detail new exciting links to the translational stress response and RNA biology that further underscore the significance of the VCP/p97 system.

Keywords: ALS; Cdc48; IBMPFD; Ubiquitin; VCP; p97.

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References

    1. Abramzon Y., Johnson J. O., Scholz S. W., Taylor J. P., Brunetti M., Calvo A., Mandrioli J., Benatar M., Mora G., Restagno G. et al. (2012). Valosin-containing protein (VCP) mutations in sporadic amyotrophic lateral sclerosis. Neurobiol. Aging 33, 2231 10.1016/j.neurobiolaging.2012.04.005 - DOI - PMC - PubMed
    1. Acs K., Luijsterburg M. S., Ackermann L., Salomons F. A., Hoppe T., Dantuma N. P. (2011). The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks. Nat. Struct. Mol. Biol. 18, 1345–1350 10.1038/nsmb.2188 - DOI - PubMed
    1. Alexandru G., Graumann J., Smith G. T., Kolawa N. J., Fang R., Deshaies R. J. (2008). UBXD7 binds multiple ubiquitin ligases and implicates p97 in HIF1alpha turnover. Cell 134, 804–816 10.1016/j.cell.2008.06.048 - DOI - PMC - PubMed
    1. Badadani M., Nalbandian A., Watts G. D., Vesa J., Kitazawa M., Su H., Tanaja J., Dec E., Wallace D. C., Mukherjee J. et al. (2010). VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease. PLoS ONE 5, e13183 10.1371/journal.pone.0013183 - DOI - PMC - PubMed
    1. Benatar M., Wuu J., Fernandez C., Weihl C. C., Katzen H., Steele J., Oskarsson B., Taylor J. P. (2013). Motor neuron involvement in multisystem proteinopathy: implications for ALS. Neurology 80, 1874–1880 10.1212/WNL.0b013e3182929fc3 - DOI - PMC - PubMed

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