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Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy

Deshaies, Raymond J. (2014) Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy. BMC Biology, 12 . Art. No. 94. ISSN 1741-7007. PMCID PMC4226866.

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Genomic alterations may make cancer cells more dependent than normal cells on mechanisms of proteostasis, including protein folding and degradation. This proposition is the basis for the clinical use of proteasome inhibitors to treat multiple myeloma and mantle cell lymphoma. However, proteasome inhibitors have not proved effective in treating other cancers, and this has called into question the general applicability of this approach. Here, I consider possible explanations for this apparently limited applicability, and discuss whether inhibiting other broadly acting components of the ubiquitin-proteasome system - including ubiquitin-activating enzyme and the AAA-ATPase p97/VCP - might be more generally effective in cancer therapy.

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Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2014 Deshaies; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated. Published online: 11 November 2014. I thank Chris Kirk, Rusty Lipford, Mark Rolfe, and Rati Verma for comments on the manuscript. I am an Investigator of the Howard Hughes Medical Institute and work in my lab on the topics covered here was supported in part by HHMI and NIH (R01CA164803, R03MH085687, R21NS071523, and R03DA032474).
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC4226866
Record Number:CaltechAUTHORS:20150122-083936041
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Official Citation:Deshaies RJ: Proteotoxic crisis, the ubiquitinproteasome system, and cancer therapy. BMC Biology 2014 12:94.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53979
Deposited By: Jason Perez
Deposited On:22 Jan 2015 20:59
Last Modified:03 Oct 2019 07:54

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