Apoptosis Regulator Bcl-2 (BCL2) Rat Recombinant Protein

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 structure: 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. Also interacts with APAF1, BBC3, BCL2L1, BNIPL, EI24, FKBP8, MRPL41, and TP53BP2. 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

By similarity. Interacts with G0S2; this interaction also prevents the formation of the anti-apoptotic BAX-BCL2 complex

By similarity.

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, with highest levels in reproductive tissues. In the adult brain, expression is localized in mitral cells of the olfactory bulb, granule and pyramidal neurons of hippocampus, pontine nuclei, cerebellar granule neurons, and in ependymal cells. In prenatal brain, expression is higher and localized in the neuroepithelium and in the cortical plate.

Domain: The BH4 motif is required for anti-apoptotic activity and for interaction with RAF1 and EGLN3

By similarity.

Post-translational modification: 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-84, wich stimulates starvation-induced autophagy

By similarity. Dephosphorylated by protein phosphatase 2A (PP2A)

By similarity.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

By similarity.Monoubiquitinated by PARK2, leading to increase its stability

By similarity.

Sequence similarities: Belongs to the Bcl-2 family.