Paradox of Bcl-2 (and p53): why may apoptosis-regulating proteins be irrelevant to cell death?
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.
Blagosklonny
M V
MV
Medicine Branch, Bldg. 10, Room 12 N 226, NIH, Bethesda, MD 20892, USA. mikhailb2box-m.nih.gov
D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53