REGULATION OF THE P53 PROTEIN BY PROTEIN-KINASE-C-ALPHA AND PROTEIN-KINASE-C-ZETA

The C-terminal of p53 (amino-acids 368-383) represses the DNA binding activity of p53. In vitro, phosphorylation of this region by Protein K inase C (PKC) is associated with increased DNA binding activity. Howev er, whether PKC can directly modulate p53 function in vivo is not know n. Here, we demonstrate that cotransfection of p53 with either PKC alp ha or PKC zeta increases p53's transcriptional activity. Mutagenesis o f p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro. Mutation of serine 371 caused a small decline i n 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 w ith either PKC alpha or PKC zeta. The results indicate that phosphoryl ation of p53 by PKC in vitro does not correlate with the ability of PK C to upregulate p53's transcriptional activity in vivo. (C) 1998 Acade mic Press.