Bcl-2-like protein 1

Function

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 (voltage-dependent anion channels (VDACs) opening. VDACs regulate 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 (Bcl-xL) acts as an apoptotic inhibitor and the shorter form (Bcl-xS) acts as an apoptotic activator.

Interactions

BCL2-like 1 (gene) has been shown to interact with:

• APAF1,
• BAK1,
• BCAP31,
• BCL2L11,
• BNIP3,
• BNIPL,
• BAD,
• BAX,
• BIK,
• Bcl-2,
• HRK,
• IKZF3,
• Noxa,
• PPP1CA,
• PSEN2
• RAD9A,
• RTN1,
• RTN4, and
• VDAC1.

References

References

1. (Aug 1993). "bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death". Cell.
2. "Entrez Gene: BCL2L1 BCL2-like 1".
3. (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of Sciences of the United States of America.
4. (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological Chemistry.
5. (Aug 2002). "Development of a high-throughput fluorescence polarization assay for Bcl-x(L)". Analytical Biochemistry.
6. (Nov 2003). "High-throughput methods to detect dimerization of Bcl-2 family proteins". Analytical Biochemistry.
7. (Jun 2005). "Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins". Genes & Development.
8. (Feb 2001). "Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL". Nature Cell Biology.
9. (Oct 1997). "p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum". The Journal of Cell Biology.
10. (Jan 1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis". The EMBO Journal.
11. (Sep 1998). "BOD (Bcl-2-related ovarian death gene) is an ovarian BH3 domain-containing proapoptotic Bcl-2 protein capable of dimerization with diverse antiapoptotic Bcl-2 members". Molecular Endocrinology.
12. (Jan 2000). "BNIP3 heterodimerizes with Bcl-2/Bcl-X(L) and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites". The Journal of Biological Chemistry.
13. (Aug 2003). "BNIPL-2, a novel homologue of BNIP-2, interacts with Bcl-2 and Cdc42GAP in apoptosis". Biochemical and Biophysical Research Communications.
14. (Feb 1999). "BNIP3alpha: a human homolog of mitochondrial proapoptotic protein BNIP3". Cancer Research.
15. (Apr 2005). "Survival function of protein kinase C{iota} as a novel nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-activated bad kinase". The Journal of Biological Chemistry.
16. (Jan 1995). "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death". Cell.
17. (Dec 2000). "Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies". Protein Science.
18. (Jul 2001). "BAD/BCL-[X(L)] heterodimerization leads to bypass of G0/G1 arrest". Oncogene.
19. (Nov 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature.
20. (Nov 2000). "PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition". Oncogene.
21. (Aug 1995). "Multiple Bcl-2 family members demonstrate selective dimerizations with Bax". Proceedings of the National Academy of Sciences of the United States of America.
22. (Jul 2003). "Induction of cell death by the BH3-only Bcl-2 homolog Nbk/Bik is mediated by an entirely Bax-dependent mitochondrial pathway". The EMBO Journal.
23. (May 2001). "Involvement of Bik, a proapoptotic member of the Bcl-2 family, in surface IgM-mediated B cell apoptosis". Journal of Immunology.
24. (Mar 1999). "The cell death-promoting gene DP5, which interacts with the BCL2 family, is induced during neuronal apoptosis following exposure to amyloid beta protein". The Journal of Biological Chemistry.
25. (Dec 2001). "The association of Aiolos transcription factor and Bcl-xL is involved in the control of apoptosis". Journal of Immunology.
26. (May 2000). "Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis". Science.
27. (Jul 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". European Journal of Immunology.
28. (Aug 1999). "Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death". The Journal of Biological Chemistry.
29. (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature.
30. (Jan 2000). "Human homologue of S. pombe Rad9 interacts with BCL-2/BCL-xL and promotes apoptosis". Nature Cell Biology.
31. (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene.
32. (Mar 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells". The Journal of Biological Chemistry.
33. (Jun 2003). "Identification of the protein-protein contact site and interaction mode of human VDAC1 with Bcl-2 family proteins". Biochemical and Biophysical Research Communications.
34. (Mar 2000). "BH4 domain of antiapoptotic Bcl-2 family members closes voltage-dependent anion channel and inhibits apoptotic mitochondrial changes and cell death". Proceedings of the National Academy of Sciences of the United States of America.
35. (Jun 1999). "Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC". Nature.