title: Regulation of the p53 protein by protein kinase C alpha and protein kinase C zeta.
abstract: The C-terminal of p53 (amino-acids 368-383) represses the DNA binding activity of p53. In vitro, phosphorylation of this region by Protein Kinase C (PKC) is associated with increased DNA binding activity. However, whether PKC can directly modulate p53 function in vivo is not known. Here, we demonstrate that cotransfection of p53 with either PKC alpha or PKC zeta increases p53's transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro. Mutation of serine 371 caused a small decline in p53 activation by PKC alpha and PKC zeta. However, the alternatively spliced murine p53, which lacks the PKC phosphorylation sites, still demonstrated increased transcriptional activation when cotransfected with either PKC alpha or PKC zeta. The results indicate that phosphorylation of p53 by PKC in vitro does not correlate with the ability of PKC to upregulate p53's transcriptional activity in vivo.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: M
authors.initials: M
authors.lastname: Youmell
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Basu
authors.forename: B D
authors.initials: BD
authors.lastname: Price
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics*; D007527:Isoenzymes / Q000494:pharmacology*; D051379:Mice; D016296:Mutagenesis / Q000235:genetics; D010766:Phosphorylation; D011493:Protein Kinase C / Q000494:pharmacology*; D051571:Protein Kinase C-alpha; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000502:physiology; D014162:Transfection / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D016159:Tumor Suppressor Protein p53; D012694:Serine; C081975:protein kinase C eta; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha