Section 19
Chapter 18,038

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

Ding, H.F.; McGill, G.; Rowan, S.; Schmaltz, C.; Shimamura, A.; Fisher, D.E.

Journal of Biological Chemistry 273(43): 28378-28383


ISSN/ISBN: 0021-9258
PMID: 9774464
DOI: 10.1074/jbc.273.43.28378
Accession: 018037606

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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.

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