Phosphorylation status and function of P53 are inversely related to protein kinase C activation.
The role of phosphorylation in the regulation of p53 protein function is little understood. We have addressed the role of protein kinase C (PKC) in the phosphorylation. Exposure to the protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), increased the phosphorylation of wild type p53 protein, whereas exposure to the tumor promoter phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), decreased it in vivo following 3 hours incubation with mouse epidermal JB6 cells. Exposure to the c-AMP dependent protein kinase (PKA) activator, forskolin, did not decrease the phosphorylation of p53 protein. In the transient transfection/luciferase reporter transactivation assay, H7 modestly increased the mouse double minute (MDM) 2 reporter transactivation activity of p53 protein after 24 hours treatment, and TPA completely blocked it. These results suggest that the accelerated phosphorylation of wild type p53 protein is inversely related to PKC activation, and that p53 phosphorylation may have some relation to transcription factor function.
Nakamura
K
K
Gene Regulation Section, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA. lfp51193@mwu.mukogawa-u.ac.jp
Sun
Y
Y
Yokoyama
Y
Y
Ferris
D
D
Singh
N
N
Ichikawa
T
T
Shinozuka
K
K
Kunitomo
M
M
Colburn
N
N
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004789:Enzyme Activation; D004817:Epidermis; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate