BCL2L2

Last updated

BCL2L2
Protein BCL2L2 PDB 1mk3.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases BCL2L2 , BCL-W, BCL2-L-2, BCLW, PPP1R51, BCL2 like 2
External IDs OMIM: 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 Mb Chr 14: 55.12 – 55.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

Function

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

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

BCL2L2 has been shown to interact with:

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000129473 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000089682 Ensembl, 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. 1 2 "Entrez Gene: BCL2L2 BCL2-like 2".
  7. 1 2 3 4 5 6 7 8 9 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. 1 2 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