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Bioessays. 2001 Oct;23(10):947-53.

Paradox of Bcl-2 (and p53): why may apoptosis-regulating proteins be irrelevant to cell death?

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  • 1Medicine Branch, Bldg. 10, Room 12 N 226, NIH, Bethesda, MD 20892, USA.


Although the Bcl-2 family members and p53 are involved in the regulation of apoptosis, the status of apoptotic machinery (eg caspases) plays a major role in determining the mode and timing of cell death. If the apoptotic machinery is lost, inhibited, or intrinsically inactivated, the "death stars", Bcl-2 and p53, may become irrelevant to cell death. In this light, high levels of Bcl-2 may indicate that downstream apoptotic pathways are still functional. This explains why Bcl-2 overexpression can be a marker of chemosensitivity and favorable prognosis in certain cancers and why retention of wild-type p53 may manifest inactivation of caspases in aggressive cancers.

Copyright 2001 John Wiley & Sons, Inc.

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