title: Regulation of the cryptic sequence-specific DNA-binding function of p53 by protein kinases.
abstract: p53 is an allosterically regulated protein with a latent DNA-binding activity. Posttranslational modification of a carboxy-terminal regulatory site in vitro, by casein kinase II and protein kinase C, can activate the sequence-specific DNA-binding function of the wild-type protein. The latent form of p53 is produced in a variety of eukaryotic and prokaryotic cell lines, including E. coli, Sf9 insect cells, and C6 cells, indicating that the activation of p53 in vivo is rate-limiting. In addition, phosphorylation of p53 at the protein kinase C site and activation in vivo correlate with the loss of reactivity of active p53 protein to the carboxy-terminal antibody, PAb421. These results suggest that two highly conserved protein kinases modify polypeptide structure through a common biochemical mechanism and that different enzymatic pathways may channel information into the carboxy-terminal regulatory site of p53, allosterically activating its function as a tumor suppressor.
authors.affiliation: Department of Biochemistry, Dundee University, Scotland.
authors.forename: T R
authors.initials: TR
authors.lastname: Hupp
authors.forename: D P
authors.initials: DP
authors.lastname: Lane
mesh_terms: D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D047390:Casein Kinase II; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D016159:Tumor Suppressor Protein p53; D004247:DNA; D011494:Protein Kinases; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C