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Protein-coding gene in the species Homo sapiens
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).[ 5] [ 6] [ 7] 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 .[ 8]
This gene encodes a pro-survival (anti-apoptotic ) member of the bcl-2 protein family , and is most similar to Bcl-xL .[ 7] 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 .[ 6] [ 9] [ 7]
Clinical significance [ edit ]
High levels of Bcl-w are seen in many cancers, including glioblastoma , colorectal cancer , non-small-cell lung carcinoma , and breast cancer .[ 7] Breast cancer patients with metastasis have higher Bcl-w than breast cancer patients only having primary tumor .[ 7] Elevated levels of Bcl-w has been shown to protect neurons from cell death induced by amyloid beta .[ 7] Parkinson's disease patients with a mutant PARK2 gene have elevated Bcl-w.[ 7] Bcl-w has been shown to contribute to cellular senescence .[ 7]
Quercetin has been shown to inhibit the PI3K/AKT pathway leading to downregulation of Bcl-w.[ 10] [ 7]
BCL2L2 has been shown to interact with:
^ Jump up to: a b c GRCh38: Ensembl release 89: ENSG00000129473 – Ensembl , May 2017
^ Jump up to: a b c GRCm38: Ensembl release 89: ENSMUSG00000089682 – Ensembl , May 2017
^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR , Baker E, Adams JM, Cory S (October 1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene . 13 (4): 665– 75. PMID 8761287 .
^ Jump up to: a b "Entrez Gene: BCL2L2 BCL2-like 2" .
^ Jump up to: a b c d e f g h i Hartman ML, Czyz M (2020). "BCL-w: apoptotic and non-apoptotic role in health and disease" . Cell Death & Disease . 11 (4): 2260. doi :10.1038/s41419-020-2417-0 . PMC 7174325 . PMID 32317622 .
^ Gibson L, Holmgreen SP, Huang DC, et al. (1996). "bcl-w, a novel member of the bcl-2 family, promotes cell survival". Oncogene . 13 (4): 665– 75. PMID 8761287 .
^ Kelly GL, Strasser A (2020). "Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy" . Annual Review of Cancer Biology . 4 : 299– 313. doi :10.1146/annurev-cancerbio-030419-033510 . hdl :11343/252362 .
^ Paez-Ribes M, González-Gualda E, Doherty GJ, Muñoz-Espín D (2019). "Targeting senescent cells in translational medicine" . EMBO Molecular Medicine . 11 (12): e10234. doi :10.15252/emmm.201810234 . PMC 6895604 . PMID 31746100 .
^ Hsu SY, Lin P, Hsueh AJ (September 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" . Mol. Endocrinol . 12 (9): 1432– 40. doi :10.1210/mend.12.9.0166 . PMID 9731710 .
^ O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (January 1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis" . EMBO J . 17 (2): 384– 95. doi :10.1093/emboj/17.2.384 . PMC 1170389 . PMID 9430630 .
^ Jump up to: a b Ayllón V, Cayla X, García A, Fleischer A, Rebollo A (July 2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad" . Eur. J. Immunol . 32 (7): 1847– 55. doi :10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 . PMID 12115603 .
^ Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC (February 2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function" . Mol. Cell . 17 (3): 393– 403. doi :10.1016/j.molcel.2004.12.030 . PMID 15694340 .
^ Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ (October 2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis . 6 (5): 319– 30. doi :10.1023/A:1011319901057 . PMID 11483855 . S2CID 23119757 .
^ Holmgreen SP, Huang DC, Adams JM, Cory S (June 1999). "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. doi :10.1038/sj.cdd.4400519 . PMID 10381646 .
Nagase T, Seki N, Ishikawa K, et al. (1997). "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. doi :10.1093/dnares/3.5.321 . PMID 9039502 .
O'Connor L, Strasser A, O'Reilly LA, et al. (1998). "Bim: a novel member of the Bcl-2 family that promotes apoptosis" . EMBO J . 17 (2): 384– 95. doi :10.1093/emboj/17.2.384 . PMC 1170389 . PMID 9430630 .
Ross AJ, Waymire KG, Moss JE, et al. (1998). "Testicular degeneration in Bclw-deficient mice". Nat. Genet . 18 (3): 251– 6. doi :10.1038/ng0398-251 . PMID 9500547 . S2CID 32843609 .
Hsu SY, Lin P, Hsueh AJ (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" . Mol. Endocrinol . 12 (9): 1432– 40. doi :10.1210/mend.12.9.0166 . PMID 9731710 .
Middleton G, Wyatt S, Ninkina N, Davies AM (2001). "Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival" . Development . 128 (3): 447– 57. doi :10.1242/dev.128.3.447 . PMID 11152643 .
O'Reilly LA, Print C, Hausmann G, et al. (2001). "Tissue expression and subcellular localization of the pro-survival molecule Bcl-w" . Cell Death Differ . 8 (5): 486– 94. doi :10.1038/sj.cdd.4400835 . PMID 11423909 .
Bae J, Hsu SY, Leo CP, et al. (2001). "Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis". Apoptosis . 6 (5): 319– 30. doi :10.1023/A:1011319901057 . PMID 11483855 . S2CID 23119757 .
Puthalakath H, Villunger A, O'Reilly LA, et al. (2001). "Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis". Science . 293 (5536): 1829– 32. Bibcode :2001Sci...293.1829P . doi :10.1126/science.1062257 . PMID 11546872 . S2CID 5638023 .
Ayllón V, Cayla X, García A, et al. (2002). "The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad" . Eur. J. Immunol . 32 (7): 1847– 55. doi :10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 . PMID 12115603 .
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 . PMC 139241 . PMID 12477932 .
Denisov AY, Madiraju MS, Chen G, et al. (2003). "Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix" . J. Biol. Chem . 278 (23): 21124– 8. doi :10.1074/jbc.M301798200 . PMID 12651847 .
Hinds MG, Lackmann M, Skea GL, et al. (2003). "The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity" . EMBO J . 22 (7): 1497– 507. doi :10.1093/emboj/cdg144 . PMC 152889 . PMID 12660157 .
Wilson-Annan J, O'Reilly LA, Crawford SA, et al. (2003). "Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity" . J. Cell Biol . 162 (5): 877– 87. doi :10.1083/jcb.200302144 . PMC 2172834 . PMID 12952938 .
Zhu X, Wang Y, Ogawa O, et al. (2004). "Neuroprotective properties of Bcl-w in Alzheimer disease" . J. Neurochem . 89 (5): 1233– 40. doi :10.1111/j.1471-4159.2004.02416.x . PMID 15147516 .
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121– 7. doi :10.1101/gr.2596504 . PMC 528928 . PMID 15489334 .
Chen L, Willis SN, Wei A, et al. (2005). "Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function" . Mol. Cell . 17 (3): 393– 403. doi :10.1016/j.molcel.2004.12.030 . PMID 15694340 .
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes" . Genome Res . 16 (1): 55– 65. doi :10.1101/gr.4039406 . PMC 1356129 . PMID 16344560 .
Denisov AY, Chen G, Sprules T, et al. (2006). "Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles". Biochemistry . 45 (7): 2250– 6. doi :10.1021/bi052332s . PMID 16475813 .
Certo M, Del Gaizo Moore V, Nishino M, et al. (2006). "Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members" . Cancer Cell . 9 (5): 351– 65. doi :10.1016/j.ccr.2006.03.027 . PMID 16697956 .
show PDB gallery
1mk3 : SOLUTION STRUCTURE OF HUMAN BCL-W PROTEIN
1o0l : THE STRUCTURE OF BCL-W REVEALS A ROLE FOR THE C-TERMINAL RESIDUES IN MODULATING BIOLOGICAL ACTIVITY
1zy3 : Structural model of complex of Bcl-w protein with Bid BH3-peptide