Cell death signal transduction and Bcl-2 function.
The mechanism by which Bcl-2 can insulate cells against multiple diverse apoptotic signals is largely undefined. How is it possible that Bcl-2, which possesses no known catalytic function, can protect against multiple cell-death signals? A proposal to address this question postulates that Bcl-2 functions at convergence points common to most cell-death signal-transduction pathways. This review attempts to integrate observations regarding cell-death signalling in an effort to define points of convergence. The ceramide/ SAPK/JNK and NF kappa B pathways, in particular, were emphasized. Potential points at which Bcl-2 may function frequently involve the transmembrane trafficking of molecules implicated in the mediation of apoptosis. The selectivity of this process and the effector proteins with which Bcl-2 associated remain to be elucidated.
Herrmann
J L
JL
University of Texas M.D. Anderson Cancer Center, Department of Molecular Pathology, Houston, TX 77030, USA.
Bruckheimer
E
E
McDonnell
T J
TJ
D000818:Animals; D017209:Apoptosis; D002451:Cell Compartmentation; D002518:Ceramides / Q000502:physiology; D019254:Genes, bcl-2; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002518:Ceramides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha