2011
DOI: 10.1007/s12013-011-9186-4
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Enzymatic Characterisation of USP7 Deubiquitinating activity and Inhibition

Abstract: USP7 (HAUSP) is a deubiquitinating enzyme, which plays a crucial role in regulating the levels of the p53 tumour suppressor protein, through its ability to prevent the proteasomal degradation of the Ubiquitin ligase for p53, Hdm2. Supporting evidence suggests that an inhibitor of USP7 would act to abrogate the action of Hdm2, and thereby elevate levels of the p53 protein, with associated therapeutic benefits in cancer and potentially other diseases. In this article, we describe the characterisation of differen… Show more

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Cited by 23 publications
(31 citation statements)
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“…The process of ubiquitination can be subverted by USPs, thus preventing the targeting of proteins to the proteasome or regulating their subcellular localization and activation . An important member of the USP family, USP7, regulates the steady‐state level of several polyubiquitinated substrates . For example, USP7 alters the level of the p53 and p16 INK4a tumor‐suppressor proteins through Mdm2 stabilization and Bmi1/melanoma nuclear protein 18 stabilization, respectively, and stabilizes DNA (cytosine 5)‐methyltransferase 1 .…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The process of ubiquitination can be subverted by USPs, thus preventing the targeting of proteins to the proteasome or regulating their subcellular localization and activation . An important member of the USP family, USP7, regulates the steady‐state level of several polyubiquitinated substrates . For example, USP7 alters the level of the p53 and p16 INK4a tumor‐suppressor proteins through Mdm2 stabilization and Bmi1/melanoma nuclear protein 18 stabilization, respectively, and stabilizes DNA (cytosine 5)‐methyltransferase 1 .…”
Section: Discussionmentioning
confidence: 99%
“…USP7 is required for several cell functions related to growth, development and stress . However, the molecular mechanisms of USP7, particularly the role of USP7 in tumorigenesis, remain to be completely defined . Recently, RNA interference (RNAi) was used to systematically screen cancer‐related USPs in the human genome .…”
mentioning
confidence: 99%
“…The full-length USP7 as well as the C-USP7 have long represented a challenge for structural studies because of their rapid degradation during recombinant expression in E. coli (43). As a consequence, difficulties in C-USP7 production hampered investigation of its structure and function.…”
Section: Isolated Usp7 Ubl Domains Can Be Studied Independently In Somentioning
confidence: 99%
“…• Deubiquitinating enzyme that cleaves ubiquitin from its substrates • Deubiquitinates and stabilizes the acetyltransferase Tip60 to induce p53-dependent apoptotic pathways Dar et al, 2013;Wrigley et al, 2011 3.3. Overexpression of miR-210 suppressed the expression of apoptotic genes…”
Section: Mir-210 Target Gene Predictionmentioning
confidence: 99%