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{{cs1 config|name-list-style=vanc}}
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Bcl-2-like protein 2''' is a 193-amino acid [[protein]] that in humans is encoded by the ''BCL2L2'' [[gene]] on [[chromosome 14]] ([[Locus (genetics)|band]] q11.2-q12).<ref name="pmid8761287">{{cite journal | vauthors = Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S | title = bcl-w, a novel member of the bcl-2 family, promotes cell survival | journal = Oncogene | volume = 13 | issue = 4 | pages = 665–75 |date=October 1996 | pmid = 8761287 | pmc = | doi = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BCL2L2 BCL2-like 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=599| accessdate = }}</ref><ref name="pmid32317622">{{cite journal | vauthors=Hartman ML, Czyz M | title=BCL-w: apoptotic and non-apoptotic role in health and disease | journal=CELL DEATH AND DISEASE | volume=11 | issue=4 | pages=2260 | year=2020 | url=https://www.nature.com/articles/s41419-020-2417-0 | doi = 10.1038/s41419-020-2417-0 | pmc=7174325 | pmid=32317622}}</ref> 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'''.<ref name="Gibson1996">{{cite journal | vauthors=Gibson L, Holmgreen SP, Huang DC |title=bcl-w, a novel member of the bcl-2 family, promotes cell survival. |journal=Oncogene |volume=13 |issue= 4 |pages= 665–75 |year= 1996 |pmid= 8761287 |doi= |display-authors=etal}}</ref>
'''Bcl-2-like protein 2''' is a 193-amino acid [[protein]] that in humans is encoded by the ''BCL2L2'' [[gene]] on [[chromosome 14]] ([[Locus (genetics)|band]] q11.2-q12).<ref name="pmid8761287">{{cite journal | vauthors = Gibson L, Holmgreen SP, Huang DC, Bernard O, Copeland NG, Jenkins NA, Sutherland GR, Baker E, Adams JM, Cory S |authorlink7=Grant Robert Sutherland | title = bcl-w, a novel member of the bcl-2 family, promotes cell survival | journal = Oncogene | volume = 13 | issue = 4 | pages = 665–75 |date=October 1996 | pmid = 8761287 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: BCL2L2 BCL2-like 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=599}}</ref><ref name="pmid32317622">{{cite journal | vauthors=Hartman ML, Czyz M | title=BCL-w: apoptotic and non-apoptotic role in health and disease | journal= Cell Death & Disease| volume=11 | issue=4 | pages=2260 | year=2020 | doi = 10.1038/s41419-020-2417-0 | pmc=7174325 | pmid=32317622}}</ref> 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'''.<ref name="Gibson1996">{{cite journal | vauthors=Gibson L, Holmgreen SP, Huang DC |title=bcl-w, a novel member of the bcl-2 family, promotes cell survival. |journal=Oncogene |volume=13 |issue= 4 |pages= 665–75 |year= 1996 |pmid= 8761287 |display-authors=etal}}</ref>


== Function ==
== Function ==
This gene encodes a pro-survival (anti-[[apoptosis|apoptotic]]) member of the [[bcl-2]] [[protein]] family. 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==
High levels of Bcl-w are seen in many cancers, including [[glioblastoma]], [[colorectal cancer]], [[non-small-cell lung carcinoma]], and [[breast cancer]].<ref name="pmid32317622" />
High levels of Bcl-w are seen in many cancers, including [[glioblastoma]], [[colorectal cancer]], [[non-small-cell lung carcinoma]], and [[breast cancer]].<ref name="pmid32317622" /> Breast cancer patients with [[metastasis]] have higher Bcl-w than breast cancer patients only having [[primary tumor]].<ref name="pmid32317622" /> Elevated levels of Bcl-w has been shown to protect [[neuron]]s from cell death induced by [[amyloid beta]].<ref name="pmid32317622" /> [[Parkinson's disease]] patients with a mutant [[Parkin (ligase)|PARK2]] gene have elevated Bcl-w.<ref name="pmid32317622" /> Bcl-w has been shown to contribute to [[cellular senescence]].<ref name="pmid32317622" />

[[Quercetin]] has been shown to inhibit the [[PI3K/AKT/mTOR pathway|PI3K/AKT pathway]] leading to [[Downregulation and upregulation|downregulation]] of Bcl-w.<ref name="pmid31746100">{{cite journal | vauthors=Paez-Ribes M, González-Gualda E, Doherty GJ, Muñoz-Espín D | title=Targeting senescent cells in translational medicine | journal=[[EMBO Molecular Medicine]] | volume=11 | issue=12 | pages=e10234 | year=2019 | doi = 10.15252/emmm.201810234 | pmc=6895604 | pmid=31746100}}</ref><ref name="pmid32317622" />


==Interactions==
==Interactions==
BCL2L2 has been shown to [[Protein-protein interaction|interact]] with:
BCL2L2 has been shown to [[Protein-protein interaction|interact]] with:
* [[BCL2L11]]<ref name="pmid9731710">{{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 |date=September 1998 | pmid = 9731710 | doi = 10.1210/mend.12.9.0166 | doi-access = free }}</ref><ref name = pmid9430630>{{cite journal | date = January 1998 | vauthors = O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC | title = Bim: a novel member of the Bcl-2 family that promotes apoptosis | journal = EMBO J. | volume = 17 | issue = 2 | pages = 384–95 | pmid = 9430630 | pmc = 1170389 | doi = 10.1093/emboj/17.2.384}}</ref>
* [[BCL2L11]]<ref name="pmid9731710">{{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 |date=September 1998 | pmid = 9731710 | doi = 10.1210/mend.12.9.0166 | doi-access = free }}</ref><ref name = pmid9430630>{{cite journal | date = January 1998 | vauthors = O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC | title = Bim: a novel member of the Bcl-2 family that promotes apoptosis | journal = EMBO J. | volume = 17 | issue = 2 | pages = 384–95 | pmid = 9430630 | pmc = 1170389 | doi = 10.1093/emboj/17.2.384}}</ref>
* [[Bcl-2-associated death promoter|BAD]],<ref name = pmid12115603/><ref name = pmid15694340>{{cite journal | date = February 2005 | vauthors = Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC | title = Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function | journal = Mol. Cell | volume = 17 | issue = 3 | pages = 393–403 | pmid = 15694340 | doi = 10.1016/j.molcel.2004.12.030}}</ref><ref name = pmid11483855>{{cite journal | date = October 2001 | vauthors = Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ | title = Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis | journal = Apoptosis | volume = 6 | issue = 5 | pages = 319–30 | pmid = 11483855 | doi = 10.1023/A:1011319901057}}</ref><ref name = pmid10381646>{{cite journal | date = June 1999 | vauthors = Holmgreen SP, Huang DC, Adams JM, Cory S | title = Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members | journal = Cell Death Differ. | volume = 6 | issue = 6 | pages = 525–32 | pmid = 10381646 | doi = 10.1038/sj.cdd.4400519| doi-access = free }}</ref> and
* [[Bcl-2-associated death promoter|BAD]],<ref name = pmid12115603/><ref name = pmid15694340>{{cite journal | date = February 2005 | vauthors = Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds MG, Colman PM, Day CL, Adams JM, Huang DC | title = Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function | journal = Mol. Cell | volume = 17 | issue = 3 | pages = 393–403 | pmid = 15694340 | doi = 10.1016/j.molcel.2004.12.030| doi-access = free }}</ref><ref name = pmid11483855>{{cite journal | date = October 2001 | vauthors = Bae J, Hsu SY, Leo CP, Zell K, Hsueh AJ | title = Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis | journal = Apoptosis | volume = 6 | issue = 5 | pages = 319–30 | pmid = 11483855 | doi = 10.1023/A:1011319901057| s2cid = 23119757 }}</ref><ref name = pmid10381646>{{cite journal | date = June 1999 | vauthors = Holmgreen SP, Huang DC, Adams JM, Cory S | title = Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members | journal = Cell Death Differ. | volume = 6 | issue = 6 | pages = 525–32 | pmid = 10381646 | doi = 10.1038/sj.cdd.4400519| doi-access = free }}</ref> and
* [[PPP1CA]].<ref name = pmid12115603>{{cite journal | date = July 2002 | vauthors = Ayllón V, Cayla X, García A, Fleischer A, Rebollo A | title = The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad | journal = Eur. J. Immunol. | volume = 32 | issue = 7 | pages = 1847–55 | pmid = 12115603 | doi = 10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7}}</ref>
* [[PPP1CA]].<ref name = pmid12115603>{{cite journal | date = July 2002 | vauthors = Ayllón V, Cayla X, García A, Fleischer A, Rebollo A | title = The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad | journal = Eur. J. Immunol. | volume = 32 | issue = 7 | pages = 1847–55 | pmid = 12115603 | doi = 10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7| doi-access = free }}</ref>


==References==
==References==
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*{{cite journal | vauthors=Nagase T, Seki N, Ishikawa K |title=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. |journal=DNA Res. |volume=3 |issue= 5 |pages= 321–9, 341–54 |year= 1997 |pmid= 9039502 |doi=10.1093/dnares/3.5.321 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Nagase T, Seki N, Ishikawa K |title=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. |journal=DNA Res. |volume=3 |issue= 5 |pages= 321–9, 341–54 |year= 1997 |pmid= 9039502 |doi=10.1093/dnares/3.5.321 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=O'Connor L, Strasser A, O'Reilly LA |title=Bim: a novel member of the Bcl-2 family that promotes apoptosis. |journal=EMBO J. |volume=17 |issue= 2 |pages= 384–95 |year= 1998 |pmid= 9430630 |doi= 10.1093/emboj/17.2.384 | pmc=1170389 |display-authors=etal}}
*{{cite journal | vauthors=O'Connor L, Strasser A, O'Reilly LA |title=Bim: a novel member of the Bcl-2 family that promotes apoptosis. |journal=EMBO J. |volume=17 |issue= 2 |pages= 384–95 |year= 1998 |pmid= 9430630 |doi= 10.1093/emboj/17.2.384 | pmc=1170389 |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 |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 |pmid= 11152643 |doi= }}
*{{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 |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}}
*{{cite journal | vauthors=Puthalakath H, Villunger A, O'Reilly LA |title=Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. |journal=Science |volume=293 |issue= 5536 |pages= 1829–32 |year= 2001 |pmid= 11546872 |doi= 10.1126/science.1062257 |display-authors=etal}}
*{{cite journal | vauthors=Puthalakath H, Villunger A, O'Reilly LA |title=Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. |journal=Science |volume=293 |issue= 5536 |pages= 1829–32 |year= 2001 |pmid= 11546872 |doi= 10.1126/science.1062257 |bibcode=2001Sci...293.1829P |s2cid=5638023 |display-authors=etal}}
*{{cite journal | vauthors=Ayllón V, Cayla X, García A |title=The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad. |journal=Eur. J. Immunol. |volume=32 |issue= 7 |pages= 1847–55 |year= 2002 |pmid= 12115603 |doi= 10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 |display-authors=etal}}
*{{cite journal | vauthors=Ayllón V, Cayla X, García A |title=The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad. |journal=Eur. J. Immunol. |volume=32 |issue= 7 |pages= 1847–55 |year= 2002 |pmid= 12115603 |doi= 10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}
*{{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Denisov AY, Madiraju MS, Chen G |title=Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix. |journal=J. Biol. Chem. |volume=278 |issue= 23 |pages= 21124–8 |year= 2003 |pmid= 12651847 |doi= 10.1074/jbc.M301798200 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Denisov AY, Madiraju MS, Chen G |title=Solution structure of human BCL-w: modulation of ligand binding by the C-terminal helix. |journal=J. Biol. Chem. |volume=278 |issue= 23 |pages= 21124–8 |year= 2003 |pmid= 12651847 |doi= 10.1074/jbc.M301798200 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Hinds MG, Lackmann M, Skea GL |title=The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. |journal=EMBO J. |volume=22 |issue= 7 |pages= 1497–507 |year= 2003 |pmid= 12660157 |doi= 10.1093/emboj/cdg144 | pmc=152889 |display-authors=etal}}
*{{cite journal | vauthors=Hinds MG, Lackmann M, Skea GL |title=The structure of Bcl-w reveals a role for the C-terminal residues in modulating biological activity. |journal=EMBO J. |volume=22 |issue= 7 |pages= 1497–507 |year= 2003 |pmid= 12660157 |doi= 10.1093/emboj/cdg144 | pmc=152889 |display-authors=etal}}
*{{cite journal | vauthors=Wilson-Annan J, O'Reilly LA, Crawford SA |title=Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity. |journal=J. Cell Biol. |volume=162 |issue= 5 |pages= 877–87 |year= 2003 |pmid= 12952938 |doi= 10.1083/jcb.200302144 | pmc=2172834 |display-authors=etal}}
*{{cite journal | vauthors=Wilson-Annan J, O'Reilly LA, Crawford SA |title=Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity. |journal=J. Cell Biol. |volume=162 |issue= 5 |pages= 877–87 |year= 2003 |pmid= 12952938 |doi= 10.1083/jcb.200302144 | pmc=2172834 |display-authors=etal}}
*{{cite journal | vauthors=Zhu X, Wang Y, Ogawa O |title=Neuroprotective properties of Bcl-w in Alzheimer disease. |journal=J. Neurochem. |volume=89 |issue= 5 |pages= 1233–40 |year= 2004 |pmid= 15147516 |doi= 10.1111/j.1471-4159.2004.02416.x |display-authors=etal}}
*{{cite journal | vauthors=Zhu X, Wang Y, Ogawa O |title=Neuroprotective properties of Bcl-w in Alzheimer disease. |journal=J. Neurochem. |volume=89 |issue= 5 |pages= 1233–40 |year= 2004 |pmid= 15147516 |doi= 10.1111/j.1471-4159.2004.02416.x |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal | vauthors=Chen L, Willis SN, Wei A |title=Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. |journal=Mol. Cell |volume=17 |issue= 3 |pages= 393–403 |year= 2005 |pmid= 15694340 |doi= 10.1016/j.molcel.2004.12.030 |display-authors=etal}}
*{{cite journal | vauthors=Chen L, Willis SN, Wei A |title=Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. |journal=Mol. Cell |volume=17 |issue= 3 |pages= 393–403 |year= 2005 |pmid= 15694340 |doi= 10.1016/j.molcel.2004.12.030 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Kimura K, Wakamatsu A, Suzuki Y |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 | pmc=1356129 |display-authors=etal}}
*{{cite journal | vauthors=Kimura K, Wakamatsu A, Suzuki Y |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 | pmc=1356129 |display-authors=etal}}
*{{cite journal | vauthors=Denisov AY, Chen G, Sprules T |title=Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles. |journal=Biochemistry |volume=45 |issue= 7 |pages= 2250–6 |year= 2006 |pmid= 16475813 |doi= 10.1021/bi052332s |display-authors=etal}}
*{{cite journal | vauthors=Denisov AY, Chen G, Sprules T |title=Structural model of the BCL-w-BID peptide complex and its interactions with phospholipid micelles. |journal=Biochemistry |volume=45 |issue= 7 |pages= 2250–6 |year= 2006 |pmid= 16475813 |doi= 10.1021/bi052332s |display-authors=etal}}
*{{cite journal | vauthors=Certo M, Del Gaizo Moore V, Nishino M |title=Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. |journal=Cancer Cell |volume=9 |issue= 5 |pages= 351–65 |year= 2006 |pmid= 16697956 |doi= 10.1016/j.ccr.2006.03.027 |display-authors=etal}}
*{{cite journal | vauthors=Certo M, Del Gaizo Moore V, Nishino M |title=Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. |journal=Cancer Cell |volume=9 |issue= 5 |pages= 351–65 |year= 2006 |pmid= 16697956 |doi= 10.1016/j.ccr.2006.03.027 |display-authors=etal|doi-access=free }}
{{Refend}}
{{Refend}}
==External links==
==External links==

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

599

12050

Ensembl

ENSG00000129473

ENSMUSG00000089682

UniProt

Q92843

P70345

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: ENSG00000129473 – Ensembl, May 2017
  2. ^ a b c 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. ^ 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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