Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Feb;22(1):T35-54.
doi: 10.1530/ERC-14-0516.

Deubiquitinases and the new therapeutic opportunities offered to cancer

Roland Pfoh  1 , Ira Kay Lacdao  1 , Vivian Saridakis  2
Affiliations
Review

Deubiquitinases and the new therapeutic opportunities offered to cancer

Roland Pfoh et al. Endocr Relat Cancer. 2015 Feb.

Abstract

Deubiquitinases (DUBs) play important roles and therefore are potential drug _targets in various diseases including cancer and neurodegeneration. In this review, we recapitulate structure-function studies of the most studied DUBs including USP7, USP22, CYLD, UCHL1, BAP1, A20, as well as ataxin 3 and connect them to regulatory mechanisms and their growing protein interaction networks. We then describe DUBs that have been associated with endocrine carcinogenesis with a focus on prostate, ovarian, and thyroid cancer, pheochromocytoma, and adrenocortical carcinoma. The goal is enhancing our understanding of the connection between dysregulated DUBs and cancer to permit the design of therapeutics and to establish biomarkers that could be used in diagnosis and prognosis.

Keywords: A20; BAP1; CYLD; UCHL1; USP22; USP7; ataxin 3; deubiquitinases.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Enzymatic cascades resulting in the ubiquitination, deubiquitination, and 26S proteasome degradation of substrate proteins.
Figure 2
Figure 2
Reactions catalyzed by deubiquitinases (DUBs). (A) Mature ubiquitin is generated following DUB cleavage. (B) DUBs recycle ubiquitin on proteins destined for degradation by the 26S proteasome. (C) DUBs deubiquitinate substrate proteins. (D) DUBs regulate ubiquitin chain editing.
Figure 3
Figure 3
Domain architecture of selected DUBs: USP7, CYLD, USP22, A20, UCHL1, BAP1, ataxin 3, and RPN11.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alimonti A, Carracedo A, Clohessy JG, Trotman LC, Nardella C, Egia A, Salmena L, Sampieri K, Haveman WJ, Brogi E, et al. Subtle variations in Pten dose determine cancer susceptibility. Nature Genetics. 2010;42:454–458. doi: 10.1038/ng.556. - DOI - PMC - PubMed
    1. Allende-Vega N, Sparks A, Lane DP, Saville MK. MdmX is a substrate for the deubiquitinating enzyme USP2a. Oncogene. 2010;29:432–441. doi: 10.1038/onc.2009.330. - DOI - PubMed
    1. Amerik AY, Hochstrasser M. Mechanism and function of deubiquitinating enzymes. Biochimica et Biophysica Acta. 2004;1695:189–207. doi: 10.1016/j.bbamcr.2004.10.003. - DOI - PubMed
    1. Aravind L, Koonin EV. The U box is a modified RING finger – a common domain in ubiquitination. Current Biology. 2000;10:R132–R134. doi: 10.1016/S0960-9822(00)00398-5. - DOI - PubMed
    1. Avvakumov GV, Walker JR, Xue S, Finerty PJ, Jr, Mackenzie F, Newman EM, Dhe-Paganon S. Amino-terminal dimerization, NRDP1–rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8) Journal of Biological Chemistry. 2006;281:38061–38070. doi: 10.1074/jbc.M606704200. - DOI - PubMed

Publication types

MeSH terms

  NODES
twitter 2