BCL2
Description
The BCL2 (BCL2 apoptosis regulator) is a protein-coding gene located on chromosome 18.
Bcl-2, encoded by the BCL2 gene in humans, is the founding member of the Bcl-2 family, a group of regulatory proteins that control programmed cell death (apoptosis). BCL2 functions as an inhibitor of apoptosis, while other members of the Bcl-2 family can either inhibit or induce apoptosis. It was the first apoptosis regulator identified in any organism. Bcl-2 is named after B-cell lymphoma 2, as it was first identified in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. Orthologs of Bcl-2 have been identified in numerous mammals. BCL2 has clinical significance in lymphoma, alongside other genes like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10. BCL2 exists in two isoforms, Isoform 1 and Isoform 2, which share a similar fold but differ in their binding to BAD and BAK proteins, structural topology, and electrostatic potential of the binding groove, leading to potential differences in their anti-apoptotic activities. BCL-2 localizes to the outer membrane of mitochondria, where it promotes cell survival and inhibits the activity of pro-apoptotic proteins. Pro-apoptotic proteins like Bax and Bak act on the mitochondrial membrane to promote its permeabilization and release of cytochrome c and ROS, both crucial signals in the apoptosis cascade.
BCL2 acts as a suppressor of apoptosis in various cell types, including factor-dependent lymphohematopoietic and neural cells. It controls cell death by regulating mitochondrial membrane permeability and appears to function in a feedback loop system with caspases. BCL2 inhibits caspase activity by preventing cytochrome c release from the mitochondria or by binding to the apoptosis-activating factor (APAF-1). BCL2 also inhibits autophagy by interacting with BECN1 and AMBRA1 during non-starvation conditions, preventing their autophagy function. BCL2 may also attenuate inflammation by impairing NLRP1-inflammasome activation, thereby reducing CASP1 activation and IL1B release.
BCL2 is also known as Bcl-2, PPP1R50.
