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BCL-2 in the crosshairs: tipping the balance of life and death Walensky LDCell Death Differ 2006[Aug]; 13 (8): 1339-50The discovery of B-cell lymphoma-2 (BCL-2) over 20 years ago revealed a new paradigm in cancer biology: the development and persistence of cancer can be driven by molecular roadblocks along the natural pathway to cell death. The subsequent identification of an expansive family of BCL-2 proteins provoked an intensive investigation of the interplay among these critical regulators of cell death. What emerged was a compelling tale of guardians and executioners, each participating in a molecular choreography that dictates cell fate. Ten years into the BCL-2 era, structural details defined how certain BCL-2 family proteins interact, and molecular targeting of the BCL-2 family has since become a pharmacological quest. Although many facets of BCL-2 family death signaling remain a mechanistic mystery, small molecules and peptides that effectively target BCL-2 are eliminating the roadblock to cell death, raising hopes for a medical breakthrough in cancer and other diseases of deregulated apoptosis.|*Apoptosis[MESH]|Animals[MESH]|Homeostasis[MESH]|Humans[MESH]|Protein Conformation[MESH]|Proto-Oncogene Proteins c-bcl-2/chemistry/classification/genetics/*metabolism[MESH]|Signal Transduction[MESH] |
