title: hsp70 binds specifically to a peptide derived from the highly conserved domain (I) region of p53.
abstract: Products of a number of mutant p53 genes bind with high affinity to members of the hsp70 family of chaperonin proteins, whereas wild type p53 lacks this type of association. Examination of the sequences of p53 genes from five different species enabled us to predict domains on p53 which may be involved in the association with hsp70 family members. A synthetic polypeptide (Pro-17-Gly) corresponding to the candidate hsp70 binding domain bound to in vitro translated hsp70 as determined by affinity chromatography and nondenaturing gel mobility shift assays. In addition, the Pro-17-Gly peptide competitively inhibited association between hsp70 and p53, an activity which was determined by immunoprecipitation with anti-p53 monoclonal antibody PAb240. The data indicate that p53 contains a hsp70 binding domain, which is located in a highly conserved region at the amino terminus of the protein, and may participate in the cellular function of wild-type p53 or in the transforming capacity of p53 mutants.
authors.affiliation: MGH Cancer Center, Harvard Medical School, Charleston, Massachusetts 02129.
authors.forename: K T
authors.initials: KT
authors.lastname: Lam
authors.forename: S K
authors.initials: SK
authors.lastname: Calderwood
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D005075:Biological Evolution; D002460:Cell Line; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D016158:Genes, p53; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis; D051381:Rats; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D010455:Peptides; D016159:Tumor Suppressor Protein p53