The Bcl-2 gene was isolated at the chromosomal breakpoint of t（14;18）-bearing follicular B cell lymphomas（1,2）.Bcl-2 blocks cell death following a variety of stimuli and confers a death-sparing effect to certain hematopoietic cell lines following growth factor withdrawal （3,5）.Bcl-2 appears to function in several subcellular locations yet lacks any known motifs that would confer insight into its mechanism of action （6,7）.A more recently identified protein,designated Bax p21（i.e., Bcl-associated X protein ）,has extensive amino acid homology with Bcl-2 and both homodimerizes and forms heterodimers with Bcl-2（8）. Overexpression of Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3 dependent cell line and Bax also counters the death repressor activty of Bcl-2（8）.

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）.
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. Interacts with EI24 （By similarity）. Also interacts with APAF1, BBC3, BCL2L1, BNIPL, MRPL41 and TP53BP2. Binding to FKBP8 seems to target BCL2 to the mitochondria and probably interferes with the binding of BCL2 to its targets. Interacts with BAG1 in an ATP-dependent manner. Interacts with RAF1 （the 'Ser-338' and 'Ser-339' phosphorylated form）. Interacts （via the BH4 domain） with EGLN3; the interaction prevents the formation of the BAX-BCL2 complex and inhibits the anti-apoptotic activity of BCL2. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex.
Subcellular Location : Mitochondrion outer membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein.
Tissue Specificity : Expressed in a variety of tissues.
Post-translational modifications : 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. Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy. Dephosphorylated by protein phosphatase 2A （PP2A）. 
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. 
Monoubiquitinated by PARK2, leading to increase its stability.
DISEASE : Note=A chromosomal aberration involving BCL2 has been found in 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.
Similarity : Belongs to the Bcl-2 family.
Database links : UniProtKB/Swiss-Prot: P10415.2 （humna）
UniProtKB/Swiss-Prot: P49950.2 （rat）
UniProtKB/Swiss-Prot: P10417.3（mouse）
Bcl-2基因是指B-cell lymphoma gene。人體濾泡B細胞淋巴瘤中過量表達的原癌基因。由于染色體t（14；18）易位，將Bcl-2基因置于免疫球蛋白重鏈的轉錄調控下，使其表達失控。在細胞系中其過量表達能延長細胞存活期而不誘導細胞增殖。它是哺乳動物中細胞調亡的抑制基因。參與細胞凋亡的調控。腫瘤中的Bcl-2基因可提高侵潤性瘤細胞的生存能力。主要用于濾胞型淋巴瘤、毛細管性白血病及細胞凋亡等方面的研究。 目前研究認為：Bcl-2也是細胞凋亡的一種抑制因子、參與細胞凋亡調控，可以用于各種惡性腫瘤的細胞凋亡的研究。