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

Prasad V. Jallepalli, Christoph Lengauer, Bert Vogelstein, 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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Tumors
Cells
Neoplasms
Checkpoint Kinase 2
Genes
Chemical activation
Phosphorylation
Homologous Recombination
Ionizing radiation
p53 Genes
Radiation damage
Transcription
Cell Cycle Checkpoints
Ionizing Radiation
Serine
Transcriptional Activation
DNA Damage
Phosphotransferases
Phenotype
Mutation

ASJC Scopus subject areas

  • Biochemistry

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The Chk2 tumor suppressor is not required for p53 responses in human cancer cells. / Jallepalli, Prasad V.; Lengauer, Christoph; Vogelstein, Bert; Bunz, Fred.

In: Journal of Biological Chemistry, Vol. 278, No. 23, 06.06.2003, p. 20475-20479.

Research output: Contribution to journalArticle

Jallepalli, Prasad V. ; Lengauer, Christoph ; Vogelstein, Bert ; Bunz, Fred. / The Chk2 tumor suppressor is not required for p53 responses in human cancer cells. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 23. pp. 20475-20479.
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