Bcl-Xl, Xs Antibody – Rabbit Polyclonal

The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 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. [provided by RefSeq, Jul 2008]

Function: Potent inhibitor of cell death. Inhibits activation of caspases

By similarity. Appears to regulate cell death by blocking the voltage-dependent anion channel (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. Ref.17 Ref.19Isoform Bcl-X(S) promotes apoptosis. Ref.17 Ref.19

Subunit structure: 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

By similarity. Interacts with BAD. 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. Isoform Bcl-X(L) interacts with BOP/C22orf29. Interacts with P53/TP53 and BBC3; interaction with BBC3 disrupts the interaction with P53/TP53. Ref.2 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.25 Ref.28 Ref.29

Subcellular location: Mitochondrion membrane; Single-pass membrane protein. Nucleus membrane; Single-pass membrane protein; Cytoplasmic side

By similarity. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome. Note: Mitochondrial membranes and perinuclear envelope

By similarity. Localizes to the centrosome when phosphorylated at Ser-49. Ref.17 Ref.19

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.

Domain: The BH4 motif is required for anti-apoptotic activity. The BH1 and BH2 motifs are required for both heterodimerization with other Bcl-2 family members and for repression of cell death.

Post-translational modification: Proteolytically cleaved by caspases during apoptosis. The cleaved protein, lacking the BH4 motif, has pro-apoptotic activity. Ref.11Phosphorylated 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 telophase and cytokinesis. Ref.17 Ref.19

Sequence similarities: Belongs to the Bcl-2 family.