Dephosphorylation of p53 during cell death by N-alpha-tosyl-L-phenylalanyl chloromethyl ketone.
The apoptotic function of N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK) was investigated in cultured human colorectal carcinoma cells (HCT116). TPCK-induced apoptosis was shown to be p53-dependent in HCT116 cells during the early stage of incubation. The function of p53 was required for TPCK-induced activation of caspase-3 and caspase-7. TPCK promoted dephosphorylation of p53 on serine residues at 6, 9, 46, 376, and 378 in parallel with the activation of p53 transcriptional activity. HCT116 p53-/- cells expressing p53 mutant, in which serine residues at 6, 9, 46, 376, and 378 were replaced by aspartic acids, were resistant to TPCK-induced apoptosis suggesting the requirement of dephosphorylation of p53 on serine residues during TPCK-induced apoptosis.
Kim
Karam
K
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejon 305-701, Republic of Korea.
Choi
Kyung Hee
KH
Fu
Ya-Min
YM
Meadows
Gary G
GG
Joe
Cheol O
CO
D017209:Apoptosis; D001224:Aspartic Acid / Q000378:metabolism; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012694:Serine / Q000378:metabolism; D013997:Time Factors; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D016159:Tumor Suppressor Protein p53; D001224:Aspartic Acid; D014108:Tosylphenylalanyl Chloromethyl Ketone; D012694:Serine; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases