A novel p53 phosphorylation site within the MDM2 ubiquitination signal: II. a model in which phosphorylation at SER269 induces a mutant conformation to p53.

ABSTRACT: The p53 DNA-binding domain harbors a conformationally flexible multiprotein binding site that regulates p53 ubiquitination. A novel phosphorylation site exists within this region at Ser(269), whose phosphomimetic mutation inactivates p53. The phosphomimetic p53 (S269D) exhibits characteristics of mutant p53: stable binding to Hsp70 in vivo, elevated ubiquitination in vivo, inactivity in DNA binding and transcription, increased thermoinstability using thermal shift assays, and λ(max) of intrinsic tryptophan fluorescence at 403 nm rather than 346 nm, characteristic of wild type p53. These data indicate that p53 conformational stability is regulated by a phosphoacceptor site within an exposed flexible surface loop and that this can be destabilized by phosphorylation. To test whether other mot

SUBMITTER: Fraser JA 

PROVIDER: S-EPMC2988382 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature