Bcl2 family
Definition: The BCL-2 family of proteins is a group of evolutionarily conserved regulators of cell death, comprising both anti- and pro-apoptotic members, which operate at the mitochondrial membrane to control caspase activation. Apoptosis is essential for maintenance of tissue homeostasis and its deregulation underlies many disease conditions.
Different BCL-2-related proteins are also located in multiprotein complexes at the endoplasmic reticulum (ER), which are involved in the control of diverse cellular processes, including calcium homeostasis, autophagy, the unfolded protein response and ER morphogenesis.
BCL-2 family proteins, which have either pro- or anti-apoptotic activities, are involved in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy.
They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host-pathogen interactions and regulate animal development.
A crucial amplificatory event in several apoptotic cascades is the nearly complete release of cytochrome-c from mitochondria.
Proteins of the BCL-2 family which include both anti- and proapoptotic members control this step. Data support a model in which the apoptotic pathway bifurcates following activation of a "BH3 only" family member.
BH3 only molecules induce the activation of the multidomain proapoptotics BAX and BAK, resulting in the permeabilization of the outer mitochondrial membrane and the efflux of cytochrome-c.
References
Hetz C, Glimcher L. The daily job of night killers: alternative roles of the BCL-2 family in organelle physiology. Trends Cell Biol. 2008 Jan;18(1):38-44. PMID: 18077169
Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59. PMID: 18097445
Scorrano L, Korsmeyer SJ. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun. 2003 May 9;304(3):437-44. PMID: 12729577
Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002 Sep;2(9):647-56. PMID: 12209154
Cory S, Adams JM: The Bcl2 family: regulators of the cellular life-or-death switch. Nature Rev Cancer 2:647, 2002.