Biology:BCL2L2
 Generic protein structure example |
Bcl-2-like protein 2 is a 193-amino acid protein that in humans is encoded by the BCL2L2 gene on chromosome 14 (band q11.2-q12).[1][2][3] It was originally discovered by Leonie Gibson, Suzanne Cory and colleagues at the Walter and Eliza Hall Institute of Medical Research, who called it Bcl-w.[4]
Function
This gene encodes a pro-survival (anti-apoptotic) member of the bcl-2 protein family, and is most similar to Bcl-xL.[3] The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis.[2][5][3]
Clinical significance
High levels of Bcl-w are seen in many cancers, including glioblastoma, colorectal cancer, non-small-cell lung carcinoma, and breast cancer.[3] Breast cancer patients with metastasis have higher Bcl-w than breast cancer patients only having primary tumor.[3] Elevated levels of Bcl-w has been shown to protect neurons from cell death induced by amyloid beta.[3] Parkinson's disease patients with a mutant PARK2 gene have elevated Bcl-w.[3] Bcl-w has been shown to contribute to cellular senescence.[3]
Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation of Bcl-w.[6][3]
Interactions
BCL2L2 has been shown to interact with:
References
- ↑ "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene 13 (4): 665–75. October 1996. PMID 8761287.
- ↑ 2.0 2.1 "Entrez Gene: BCL2L2 BCL2-like 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=599.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 "BCL-w: apoptotic and non-apoptotic role in health and disease". Cell Death & Disease 11 (4): 2260. 2020. doi:10.1038/s41419-020-2417-0. PMID 32317622.
- ↑ "bcl-w, a novel member of the bcl-2 family, promotes cell survival.". Oncogene 13 (4): 665–75. 1996. PMID 8761287.
- ↑ Kelly, Gemma L.; Strasser, Andreas (2020). "Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy". Annual Review of Cancer Biology 4: 299–313. doi:10.1146/annurev-cancerbio-030419-033510.
- ↑ "Targeting senescent cells in translational medicine". EMBO Molecular Medicine 11 (12): e10234. 2019. doi:10.15252/emmm.201810234. PMID 31746100.
- ↑ "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". Mol. Endocrinol. 12 (9): 1432–40. September 1998. doi:10.1210/mend.12.9.0166. PMID 9731710.
- ↑ "Bim: a novel member of the Bcl-2 family that promotes apoptosis". EMBO J. 17 (2): 384–95. January 1998. doi:10.1093/emboj/17.2.384. PMID 9430630.
- ↑ 9.0 9.1 "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad". Eur. J. Immunol. 32 (7): 1847–55. July 2002. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.
- ↑ "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function". Mol. Cell 17 (3): 393–403. February 2005. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
- ↑ "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis 6 (5): 319–30. October 2001. doi:10.1023/A:1011319901057. PMID 11483855.
- ↑ "Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members". Cell Death Differ. 6 (6): 525–32. June 1999. doi:10.1038/sj.cdd.4400519. PMID 10381646.
Further reading
- "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.". DNA Res. 3 (5): 321–9, 341–54. 1997. doi:10.1093/dnares/3.5.321. PMID 9039502.
- "Bim: a novel member of the Bcl-2 family that promotes apoptosis.". EMBO J. 17 (2): 384–95. 1998. doi:10.1093/emboj/17.2.384. PMID 9430630.
- "Testicular degeneration in Bclw-deficient mice.". Nat. Genet. 18 (3): 251–6. 1998. doi:10.1038/ng0398-251. PMID 9500547.
- "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.". Mol. Endocrinol. 12 (9): 1432–40. 1998. doi:10.1210/mend.12.9.0166. PMID 9731710.
- "Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival.". Development 128 (3): 447–57. 2001. doi:10.1242/dev.128.3.447. PMID 11152643.
- "Tissue expression and subcellular localization of the pro-survival molecule Bcl-w.". Cell Death Differ. 8 (5): 486–94. 2001. doi:10.1038/sj.cdd.4400835. PMID 11423909.
- "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis.". Apoptosis 6 (5): 319–30. 2001. doi:10.1023/A:1011319901057. PMID 11483855.
- "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis.". Science 293 (5536): 1829–32. 2001. doi:10.1126/science.1062257. PMID 11546872. Bibcode: 2001Sci...293.1829P.
- "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad.". Eur. J. Immunol. 32 (7): 1847–55. 2002. doi:10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7. PMID 12115603.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix.". J. Biol. Chem. 278 (23): 21124–8. 2003. doi:10.1074/jbc.M301798200. PMID 12651847.
- "The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity.". EMBO J. 22 (7): 1497–507. 2003. doi:10.1093/emboj/cdg144. PMID 12660157.
- "Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity.". J. Cell Biol. 162 (5): 877–87. 2003. doi:10.1083/jcb.200302144. PMID 12952938.
- "Neuroprotective properties of Bcl-w in Alzheimer disease.". J. Neurochem. 89 (5): 1233–40. 2004. doi:10.1111/j.1471-4159.2004.02416.x. PMID 15147516.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.". Mol. Cell 17 (3): 393–403. 2005. doi:10.1016/j.molcel.2004.12.030. PMID 15694340.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles.". Biochemistry 45 (7): 2250–6. 2006. doi:10.1021/bi052332s. PMID 16475813.
- "Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members.". Cancer Cell 9 (5): 351–65. 2006. doi:10.1016/j.ccr.2006.03.027. PMID 16697956.
External links
- Human BCL2L2 genome location and BCL2L2 gene details page in the UCSC Genome Browser.
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