BCL-2 gene family and the regulation of programmed cell death.

摘要: The BCL-2 gene was identified at the chromosomal breakpoint of t(14; 18)-bearing human follicular B cell lymphomas. proved to block programmed death rather than promote proliferation. Transgenic mice that overexpress Bcl-2 in lineage demonstrate extended survival and progress high-grade Thus, initiated a new category oncogenes, regulators death. Bcl-2-deficient fulminant apoptosis lymphocytes, profound renal loss melanocytes. protein duels with its counteracting twin, partner known as BAX. When BAX is excess, cells execute command; but, when dominates, program inhibited survive. Bax-deficient display cellular hyperplasia, confirming role proapoptotic molecule. An expanded family BCL-2-related proteins shares homology clustered within four conserved regions termed 1 through 4 (BH1-4). These novel domains control ability these dimerize function. amphipathic alpha helix, BH3, particular importance for members. BID BAD represent an evolving set molecules, which bear sequence only BH3. They appear reside more proximal pathway serving ligands. connects upstream signal transduction paths family, modulating this checkpoint apoptosis. In presence factor interleukin-3, phosphorylate on two serine residues. This inactivated held by 14-3-3 protein, freeing BCL-XL survival. Activation results initiation Downstream events include mitochondrial dysfunction, well Caspase activation. pro- antiapoptotic members central evolutionarily Aberrations result disordered homeostasis, pathogenic event diseases, including cancer.