Editors' ChoiceApoptosis

Cytosolic Role of p53

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Science's STKE  17 Feb 2004:
Vol. 2004, Issue 220, pp. tw64-TW64
DOI: 10.1126/stke.2202004TW64

The tumor suppressor protein p53 promotes apoptosis of tumor cells. Although p53 functions as a transcription factor, it appears to have important cytosolic effects that are independent of its effects in the nucleus. Chipuk et al. find that p53 directly enhances permeabilization of mitochondria by the proapoptotic protein Bax. In vitro or in transfected cells, p53 also caused release of proapoptotic proteins that are normally sequestered by binding to the antiapoptotic protein Bcl-xL. The cytosolic effects of p53 appear to be functionally important because p53 still promoted apoptosis in cells in which nuclear transport of p53 and consequent transcriptional regulation were blocked.

J. E. Chipuk, T. Kuwana, L. Bouchier-Hayes, N. M. Droin, D. D. Newmeyer, M. Schuler, D. R. Green, Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303, 1010-1014 (2004). [Abstract] [Full Text]

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