Dephosphorylation of p53 during cell death by N-alpha-tosyl-L-phenylalanyl chloromethyl ketone

Biochem Biophys Res Commun. 2003 Jul 11;306(4):954-8. doi: 10.1016/s0006-291x(03)01088-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Aspartic Acid / metabolism
  • Caspase 3
  • Caspase 7
  • Caspases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Genes, p53*
  • Humans
  • Mutation
  • Phosphorylation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Synthesis Inhibitors / pharmacology*
  • Serine / metabolism
  • Time Factors
  • Tosylphenylalanyl Chloromethyl Ketone / pharmacology*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Enzyme Inhibitors
  • Protein Synthesis Inhibitors
  • Tumor Suppressor Protein p53
  • Aspartic Acid
  • Tosylphenylalanyl Chloromethyl Ketone
  • Serine
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7
  • Caspases