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{{cs1 config|name-list-style=vanc}}
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
{{Infobox_gene}}
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== Function ==
== Function ==
This gene encodes a pro-survival (anti-[[apoptosis|apoptotic]]) member of the [[Bcl-2 family| bcl-2 protein family]], and is most similar to [[Bcl-xL]].<ref name="pmid32317622" /> 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 [[cytotoxicity|cytotoxic]] conditions. Studies of the related gene in mice indicated a role in the survival of [[Nerve growth factor|NGF]]- and [[BDNF]]-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult [[spermatogenesis]].<ref name="entrez"/><ref>{{cite journal|doi=10.1146/annurev-cancerbio-030419-033510|doi-access=free|title=Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy|year=2020|last1=Kelly|first1=Gemma L.|last2=Strasser|first2=Andreas|journal=Annual Review of Cancer Biology|volume=4|pages=299–313}}</ref><ref name="pmid32317622" />
This gene encodes a pro-survival (anti-[[apoptosis|apoptotic]]) member of the [[Bcl-2 family| bcl-2 protein family]], and is most similar to [[Bcl-xL]].<ref name="pmid32317622" /> 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 [[cytotoxicity|cytotoxic]] conditions. Studies of the related gene in mice indicated a role in the survival of [[Nerve growth factor|NGF]]- and [[BDNF]]-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult [[spermatogenesis]].<ref name="entrez"/><ref>{{cite journal|doi=10.1146/annurev-cancerbio-030419-033510|doi-access=free|title=Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy|year=2020|last1=Kelly|first1=Gemma L.|last2=Strasser|first2=Andreas|journal=Annual Review of Cancer Biology|volume=4|pages=299–313|hdl=11343/252362|hdl-access=free}}</ref><ref name="pmid32317622" />


== Clinical significance==
== Clinical significance==
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*{{cite journal | vauthors=Ross AJ, Waymire KG, Moss JE |title=Testicular degeneration in Bclw-deficient mice. |journal=Nat. Genet. |volume=18 |issue= 3 |pages= 251–6 |year= 1998 |pmid= 9500547 |doi= 10.1038/ng0398-251 |s2cid=32843609 |display-authors=etal}}
*{{cite journal | vauthors=Ross AJ, Waymire KG, Moss JE |title=Testicular degeneration in Bclw-deficient mice. |journal=Nat. Genet. |volume=18 |issue= 3 |pages= 251–6 |year= 1998 |pmid= 9500547 |doi= 10.1038/ng0398-251 |s2cid=32843609 |display-authors=etal}}
*{{cite journal | vauthors=Hsu SY, Lin P, Hsueh AJ |title=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. |journal=Mol. Endocrinol. |volume=12 |issue= 9 |pages= 1432–40 |year= 1998 |pmid= 9731710 |doi=10.1210/mend.12.9.0166 |doi-access=free }}
*{{cite journal | vauthors=Hsu SY, Lin P, Hsueh AJ |title=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. |journal=Mol. Endocrinol. |volume=12 |issue= 9 |pages= 1432–40 |year= 1998 |pmid= 9731710 |doi=10.1210/mend.12.9.0166 |doi-access=free }}
*{{cite journal | vauthors=Middleton G, Wyatt S, Ninkina N, Davies AM |title=Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival. |journal=Development |volume=128 |issue= 3 |pages= 447–57 |year= 2001 |doi=10.1242/dev.128.3.447 |pmid= 11152643 }}
*{{cite journal | vauthors=Middleton G, Wyatt S, Ninkina N, Davies AM |title=Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival. |journal=Development |volume=128 |issue= 3 |pages= 447–57 |year= 2001 |doi=10.1242/dev.128.3.447 |pmid= 11152643 |url=http://dev.biologists.org/content/128/3/447.abstract }}
*{{cite journal | vauthors=O'Reilly LA, Print C, Hausmann G |title=Tissue expression and subcellular localization of the pro-survival molecule Bcl-w. |journal=Cell Death Differ. |volume=8 |issue= 5 |pages= 486–94 |year= 2001 |pmid= 11423909 |doi= 10.1038/sj.cdd.4400835 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=O'Reilly LA, Print C, Hausmann G |title=Tissue expression and subcellular localization of the pro-survival molecule Bcl-w. |journal=Cell Death Differ. |volume=8 |issue= 5 |pages= 486–94 |year= 2001 |pmid= 11423909 |doi= 10.1038/sj.cdd.4400835 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Bae J, Hsu SY, Leo CP |title=Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. |journal=Apoptosis |volume=6 |issue= 5 |pages= 319–30 |year= 2001 |pmid= 11483855 |doi=10.1023/A:1011319901057 |s2cid=23119757 |display-authors=etal}}
*{{cite journal | vauthors=Bae J, Hsu SY, Leo CP |title=Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. |journal=Apoptosis |volume=6 |issue= 5 |pages= 319–30 |year= 2001 |pmid= 11483855 |doi=10.1023/A:1011319901057 |s2cid=23119757 |display-authors=etal}}

Latest revision as of 06:07, 15 January 2024

BCL2L2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBCL2L2, BCL-W, BCL2-L-2, BCLW, PPP1R51, BCL2 like 2
External IDsOMIM: 601931; MGI: 108052; HomoloGene: 2989; GeneCards: BCL2L2; OMA:BCL2L2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004050
NM_001199839

NM_007537

RefSeq (protein)

NP_001186768
NP_004041

NP_031563

Location (UCSC)Chr 14: 23.3 – 23.31 MbChr 14: 55.12 – 55.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Function

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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

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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]

Interactions

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BCL2L2 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000129473Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000089682Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b "Entrez Gene: BCL2L2 BCL2-like 2".
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.

Further reading

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