title: Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6.
abstract: In vitro, high-risk human papillomavirus E6 proteins have been shown, in conjunction with E6-associated protein (E6AP), to mediate ubiquitination of p53 and its degradation by the 26S proteasome by a pathway that is thought to be analogous to Mdm2-mediated p53 degradation. However, differences in the requirements of E6/E6AP and Mdm2 to promote the degradation of p53, both in vivo and in vitro, suggest that these two E3 ligases may promote p53 degradation by distinct pathways. Using tools that disrupt ubiquitination and degradation, clear differences between E6- and Mdm2-mediated p53 degradation are presented. The consistent failure to fully protect p53 protein from E6-mediated degradation by disrupting the ubiquitin-degradation pathway provides the first evidence of an E6-dependent, ubiquitin-independent, p53 degradation pathway in vivo.
authors.affiliation: Department of Cell Cycle Control, Institute of Molecular and Cell Biology, Proteos, Singapore. scamus@imcb.a-star.edu.sg
authors.forename: S
authors.initials: S
authors.lastname: Camus
authors.forename: S
authors.initials: S
authors.lastname: Menéndez
authors.forename: C F
authors.initials: CF
authors.lastname: Cheok
authors.forename: L F
authors.initials: LF
authors.lastname: Stevenson
authors.forename: S
authors.initials: S
authors.lastname: Laín
authors.forename: D P
authors.initials: DP
authors.lastname: Lane
mesh_terms: D000818:Animals; D002460:Cell Line; D006868:Hydrolysis; D051379:Mice; D027383:Papillomaviridae / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D014764:Viral Proteins