Stepwise multipolyubiquitination of p53 by the E6AP-E6 ubiquitin ligase complex
نویسندگان
چکیده
منابع مشابه
Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin ligase complex by the HECT domain-containing protein EDD.
Human papillomavirus (HPV) E6 oncoproteins target many cellular proteins for ubiquitin-mediated proteasomal degradation. In the case of p53, this is mediated principally by the E6AP ubiquitin ligase. Several studies have reported that E6 can target certain of its substrates in an apparently E6AP-independent fashion and that several of these substrates vary in the degree to which they are degrad...
متن کاملHuman papillomavirus E6-induced degradation of E6TP1 is mediated by E6AP ubiquitin ligase.
High-risk human papilloma viruses are known to be associated with cervical cancers. We have reported previously that the high-risk human papillomavirus (HPV) E6 oncoprotein interacts with E6TP1, a novel Rap GTPase-activating protein (RapGAP). Similar to p53 tumor suppressor protein, the high-risk HPV E6 oncoproteins target E6TP1 for degradation. The HPV16 E6-induced degradation of E6TP1 strongl...
متن کاملHuman papillomavirus type 16 E6 induces self-ubiquitination of the E6AP ubiquitin-protein ligase.
The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is sta...
متن کاملGRIM-19 Disrupts E6/E6AP Complex to Rescue p53 and Induce Apoptosis in Cervical Cancers
BACKGROUND Our previous studies showed a down-regulation of GRIM-19 in primary human cervical cancers, and restoration of GRIM-19 induced tumor regression. The induction of tumor suppressor protein p53 ubiquitination and degradation by E6 oncoportein of high risk-HPV through forming a stable complex with E6AP is considered as a critical mechanism for cervical tumor development. The aims of this...
متن کاملStructure and function of the papillomavirus E6 protein and its interacting proteins.
Infection by high risk papillomavirus causes various forms of anogenital cancer including squamous cell carcinoma of the cervix. A primary step in the carcinogenesis includes formation of a complex of viral E6 protein and a human E3 ubiquitin ligase. This complex is competent to cause degradation and inactivation of several target proteins including human tumor suppressors which contributes to ...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2019
ISSN: 0021-9258
DOI: 10.1074/jbc.ra119.008374