The Chk2 tumor suppressor is not required for p53 responses in human cancer cells

Prasad V. Jallepalli, Christoph Lengauer, Bert Vogelsteint, Fred Bunz

Research output: Contribution to journalArticle

Abstract

Ionizing radiation damages chromosomal DNA and activates p53-dependent transcription in mammalian cells. The Chk2 protein kinase has been hypothesized to be the primary mediator of this response. We have rigorously tested this hypothesis in human cells by disrupting the CHK2 gene through homologous recombination. We found that the p53 response was unexpectedly robust in such cells. Phosphorylation of p53 at serine 20, accumulation of p53 protein, transcriptional activation of p53 target genes, and cell cycle arrest and apoptotic death phenotypes were completely intact regardless of CHK2 status. Our results indicate that Chk2 kinase is not required for p53 activation in human cells and explain why CHK2 and TP53 mutations can jointly occur in human tumors.

Original languageEnglish (US)
Pages (from-to)20475-20479
Number of pages5
JournalJournal of Biological Chemistry
Volume278
Issue number23
DOIs
StatePublished - Jun 6 2003

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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