2008
DOI: 10.1074/jbc.m708278200
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USP11 Stabilizes HPV-16E7 and Further Modulates the E7 Biological Activity

Abstract: HPV-16E7 is a major transforming protein, which has been implicated in the development of cervical cancer. The stability of E7 is thus important to ensure its fully functional status. Using the yeast two-hybrid system, we found that USP11 (ubiquitin-specific protease 11), a member of a protein family that cleaves polyubiquitin chains and/or ubiquitin precursors, interacts and forms a specific complex with HPV-16E7. Our results indicate that the USP11 can greatly increase the steady state level of HPV-16E7 by r… Show more

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Cited by 50 publications
(43 citation statements)
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“…USP7 is known to regulate the cellular turnover of p53 (26), suggesting that these herpesviruses may be able to manipulate the apoptotic status of infected cells through interaction with USP7. Binding of USP11 has been reported to stabilize HPV16 E7 through deubiquitylation, extending its half-life and enhancing the downstream degradation of Rb (27). In addition, HPV16 and HPV18 E6 proteins have been implicated in the ubiquitylation and degradation of the CYLD DUB, resulting in the sustained hypoxia-induced activation of NF-B (1).…”
Section: Discussionmentioning
confidence: 99%
“…USP7 is known to regulate the cellular turnover of p53 (26), suggesting that these herpesviruses may be able to manipulate the apoptotic status of infected cells through interaction with USP7. Binding of USP11 has been reported to stabilize HPV16 E7 through deubiquitylation, extending its half-life and enhancing the downstream degradation of Rb (27). In addition, HPV16 and HPV18 E6 proteins have been implicated in the ubiquitylation and degradation of the CYLD DUB, resulting in the sustained hypoxia-induced activation of NF-B (1).…”
Section: Discussionmentioning
confidence: 99%
“…Mitoxantrone has been used previously for the treatment of pancreatic cancer. A pair of dated European trials from Beger and colleagues compared celiac artery infusion of mitoxantrone, 5-FU, folinic acid, and cisplatinum in patients with resected pancreatic ductal adenocarcinoma (53,54). Both studies were small (<30 patients) and single-arm studies, in comparison with historical institutional control patients who did not receive any adjuvant treatment.…”
Section: Discussionmentioning
confidence: 99%
“…E7 binds to USP11, which reduces the ubiquitination and therefore enhances the stability of E7. 52 Thus, the stability of E7 depends on the net result of two opposing activities controlling the rate of ubiquitination. In addition to E7, HPV E2 and E6 have both been reported to be ubiquitinated and degraded by the proteasome.…”
Section: Hpv Proteins Degraded By E3 Ubiquitin Ligasesmentioning
confidence: 99%