Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free system

Han Fei Ding, Gaël McGill, Sheldon Rowan, Cornelius Schmaltz, Akiko Shimamura, David E. Fisher

Research output: Contribution to journalArticle

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Abstract

The mechanism by which p53 modulates apoptosis in cancer therapy is incompletely understood. Here, cell-free extracts from irradiated tumor cells are described in which endogenous p53 protein is shown to participate in caspase activation. This apoptotic activity is also oncogene-dependent, but independent of transcription in general or the presence of Bax or cytochrome c. A general use for this system is as a cell-free screen for apoptosis modulators. In this way, profound effects of protein kinase A were identified and corroborated in vivo by the protection conferred by cAMP against diverse triggers of p53-dependent apoptosis. This system provides direct biochemical evidence that p53 protein can transduce apoptotic signals through protein- protein interactions and reveals a modulator kinase pathway capable of regulating p53-dependent caspase activation.

Original languageEnglish (US)
Pages (from-to)28378-28383
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number43
DOIs
Publication statusPublished - Oct 23 1998
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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