The protein encoded by this gene belongs to the Bcl2 protein family. Bcl2 family members form hetero or homodimers and act as anti or pro apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported. The longer isoform acts as an apoptotic inhibitor and the shorter form acts as an apoptotic activator. Alternative names: Apoptosis regulator Bcl X ; Apoptosis regulator BclX; B cell lymphoma 2 like; Bcl 2 like 1 protein; Bcl X; Bcl xL; BCL XL/S; Bcl xS; Bcl2 Like 1; Bcl2 related gene; BCL2L; Bcl2l1; BCLX; BclXL; BclXs; DKFZp781P2092.
Function : Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channnel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.
Isoform Bcl-X(S) promotes apoptosis.
Subunit : Homodimer. Isoform Bcl-X(L) forms heterodimers with BAX, BAK or BCL2. Heterodimerization with BAX does not seem to be required for anti-apoptotic activity. Interacts with BCL2L11. Interacts with DMN1L; the interaction stimulates the GTPase activity of DMN1L in synapses and increases the number of axonal mitochondria and the size and number of synaptic vesicle clusters. Interacts with BAD and BBC3. Interacts (isoform Bcl-X(L)) with SIVA1 (isoform 1); the interaction inhibits the anti-apoptotic activity. Interacts with BECN1 and PGAM5. Interacts (isoform Bcl-X(L)) with BAX (isoform Sigma). Isoform Bcl-X(L) interacts with IKZF3. Interacts with HEBP2.
Subcellular Location : Mitochondrion membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein; Cytoplasmic side. Cytoplasm, cytoskeleton, centrosome. Note=Mitochondrial membranes and perinuclear envelope. Localizes to the centrosome when phosphorylated at Ser-49.
Tissue Specificity : Bcl-X(S) is expressed at high levels in cells that undergo a high rate of turnover, such as developing lymphocytes. In contrast, Bcl-X(L) is found in tissues containing long-lived postmitotic cells, such as adult brain.
Post-translational modifications : Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity.
Phosphorylated on Ser-62 by CDK1. This phosphorylation is partial in normal mitotic cells, but complete in G2-arrested cells upon DNA-damage, thus promoting subsequent apoptosis probably by triggering caspases-mediated proteolysis. Phosphorylated by PLK3, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Phosphorylation at Ser-49 appears during the S phase and G2, disappears rapidly in early mitosis during prometaphase, metaphase and early anaphase, and re-appears during ophase and cytokinesis.
Similarity : Belongs to the Bcl-2 family.
Bcl X/L蛋白是Bcl蛋白家族的成員之一,是細胞中抑制細胞凋亡的重要分子之一,Bcl-X/L是結(jié)構(gòu)上與Bcl-2具有43%同源性的蛋白,與Bcl-2的作用相同,可抑制細胞凋亡,在腫瘤的發(fā)生和發(fā)展中起重要作用。