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

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Abstract
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. BioEssays 23:947–953, 2001. © 2001 John Wiley & Sons, Inc.