Identification of a region of p53 that confers lability.
Degradation provides one means for controlling the cellular level of the p53 tumor suppressor. Here we have determined a structural element of p53 required for degradation. To create a substrate amenable to in vitro analysis of proteolysis, we appended to p53 the N terminus of antizyme, a protein that binds to and induces degradation of mammalian ornithine decarboxylase (ODC). We found using deletion analysis that an element within amino acids 100-150 is required for degradation of the fusion protein. A monoclonal antibody (PAb246) that binds close to this region prevents the degradation induced by human papillomavirus 16 E6 protein. Furthermore, we found that amino acids 100-150 of p53 can function as an independent domain to induce Trypanosoma brucei ODC, a stable protein, to be degraded in vivo or, by cooperating with an antizyme binding domain of ODC, to confer polyamine-dependent regulation.
Li
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Department of Microbiology and Immunology, University of California, San Francisco, 94143, USA.
Coffino
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D000818:Animals; D000911:Antibodies, Monoclonal; D006801:Humans; D007700:Kinetics; D008322:Mammals; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D009955:Ornithine Decarboxylase