Disease:A chromosomal aberration involving BCL2 may be a cause of follicular lymphoma (FL) [MIM:151430]; also known as type II chronic lymphatic leukemia. Translocation t (14;18) (q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. ,Domain:The BH4 motif is required for anti-apoptotic activity and for interaction with RAF-1. ,Function:Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1) . ,online information:Bcl-2 entry ,PTM:Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity. Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle. In the absence of growth factors , BCL2 appears to be phosphorylated by other protein kinases such as ERKs and stress-activated kinases. Dephosphorylated by protein phosphatase 2A (PP2A) . ,PTM:Proteolytically cleaved by caspases during apoptosis. The cleaved protein , lacking the BH4 motif , has pro-apoptotic activity , causes the release of cytochrome c into the cytosol promoting further caspase activity. ,similarity:Belongs to the Bcl-2 family. ,subunit:Forms homodimers , and heterodimers with BAX , BAD , BAK and Bcl-X (L) . Heterodimerization with BAX requires intact BH1 and BH2 motifs , and is necessary for anti-apoptotic activity (By similarity) . Also interacts with APAF1 , RAF-1 , TP53BP2 , BBC3 , BCL2L1 , MRPL41 and BNIPL. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. ,tissue specificity:Expressed in a variety of tissues. ,
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