title: The p53 isoforms are differentially modified by Mdm2.
abstract: The discovery that the single p53 gene encodes several different p53 protein isoforms has initiated a flurry of research into the function and regulation of these novel p53 proteins. Full-length p53 protein level is primarily regulated by the E3-ligase Mdm2, which promotes p53 ubiquitination and degradation. Here, we report that all of the novel p53 isoforms are ubiquitinated and degraded to varying degrees in an Mdm2-dependent and -independent manner, and that high-risk human papillomavirus can degrade some but not all of the novel isoforms, demonstrating that full-length p53 and the p53 isoforms are differentially regulated. In addition, we provide the first evidence that Mdm2 promotes the NEDDylation of p53β. Altogether, our data indicates that Mdm2 can distinguish between the p53 isoforms and modify them differently.
authors.affiliation: Institute of Molecular and Cell Biology, Singapore.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Camus
authors.forename: Sergio
authors.initials: S
authors.lastname: Ménendez
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fernandes
authors.forename: Nelly
authors.initials: N
authors.lastname: Kua
authors.forename: Geng
authors.initials: G
authors.lastname: Liu
authors.forename: Dimitris P
authors.initials: DP
authors.lastname: Xirodimas
authors.forename: David P
authors.initials: DP
authors.lastname: Lane
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Bourdon
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D007976:Leupeptins / Q000737:chemistry / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D007976:Leupeptins; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde