BCL2L11
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{cs1 config|name-list-style=vanc}}
{{Infobox_gene}}
Bcl-2-like protein 11, commonly called BIM (Bcl-2 Interacting Mediator of cell death), is a protein that in humans is encoded by the BCL2L11 gene.{{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=November 1998| pmid = 9731710 | doi =10.1210/mend.12.9.0166 | doi-access = free }}{{cite journal | 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 | date=February 1998| pmid = 9430630 | pmc = 1170389 | doi = 10.1093/emboj/17.2.384 }}
Function
The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family, including BCL2, BCL2L1/BCL-X(L), and MCL1, and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1 (FoxO3a), which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified.{{cite web | title = Entrez Gene: BCL2L11 BCL2-like 11 (apoptosis facilitator)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10018}}
= Regulation of Bim =
Bim expression and activity are regulated at the transcriptional, translational and post-translational levels; coordinated expression and activity of Bim shape immune responses, and ensure tissue integrity. Cancer cells develop mechanisms that suppress Bim expression, which allows for tumor progression and metastasis.{{cite journal |vauthors = Sionov RV, Vlahopoulos SA, Granot Z |title = Regulation of Bim in Health and Disease |journal = Oncotarget |volume = 6 |issue = 27 |pages = 23058–134 |year = 2015 |pmid = 26405162 |pmc = 4695108 |doi = 10.18632/oncotarget.5492 }}
Interactions
BCL2L11 has been shown to interact with:
- BCL2-like 1,{{cite journal | date = November 2003 | vauthors = Whitfield J, Harada K, Bardelle C, Staddon JM | title = High-throughput methods to detect dimerization of Bcl-2 family proteins | journal = Anal. Biochem. | volume = 322 | issue = 2 | pages = 170–8 | pmid = 14596824 | doi = 10.1016/j.ab.2003.07.014}}
- BCL2L2,
- Bcl-2,
- DYNLL1,{{cite journal | date = February 2004 | vauthors = Day CL, Puthalakath H, Skea G, Strasser A, Barsukov I, Lian LY, Huang DC, Hinds MG | title = Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands | journal = Biochem. J. | volume = 377 | issue = Pt 3 | pages = 597–605 | pmid = 14561217 | pmc = 1223895 | doi = 10.1042/BJ20031251}}{{cite journal | date = June 2004 | vauthors = Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R | title = Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes | journal = Cancer Cell | volume = 5 | issue = 6 | pages = 575–85 | pmid = 15193260 | doi = 10.1016/j.ccr.2004.05.022| doi-access = free }} and
- MCL1.{{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 }}{{cite journal | date = August 2000 | vauthors = Bae J, Leo CP, Hsu SY, Hsueh AJ | title = MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain | journal = J. Biol. Chem. | volume = 275 | issue = 33 | pages = 25255–61 | pmid = 10837489 | doi = 10.1074/jbc.M909826199| doi-access = free }}{{cite journal |last1=Heckmeier |first1=Philipp J. |last2=Ruf |first2=Jeannette |last3=Buhrke |first3=David |last4=Janković |first4=Brankica G. |last5=Hamm |first5=Peter |title=Signal Propagation Within the MCL-1/BIM Protein Complex |journal=Journal of Molecular Biology |date=September 2022 |volume=434 |issue=17 |pages=167499 |doi=10.1016/j.jmb.2022.167499|pmid=35189130 |doi-access=free }}
See also
References
{{reflist}}
Further reading
{{refbegin | 2}}
- {{cite journal | vauthors=Wang K, Yin XM, Chao DT |title=BID: a novel BH3 domain-only death agonist |journal=Genes Dev. |volume=10 |issue= 22 |pages= 2859–69 |year= 1996 |pmid= 8918887 |doi=10.1101/gad.10.22.2859 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Zha J, Harada H, Yang E |title=Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L) |journal=Cell |volume=87 |issue= 4 |pages= 619–28 |year= 1997 |pmid= 8929531 |doi=10.1016/S0092-8674(00)81382-3 |s2cid=860908 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Huang DC, Adams JM, Cory S |title=The conserved N-terminal BH4 domain of Bcl-2 homologues is essential for inhibition of apoptosis and interaction with CED-4 |journal=EMBO J. |volume=17 |issue= 4 |pages= 1029–39 |year= 1998 |pmid= 9463381 |doi= 10.1093/emboj/17.4.1029 | pmc=1170452 }}
- {{cite journal | vauthors=Puthalakath H, Huang DC, O'Reilly LA |title=The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex |journal=Mol. Cell |volume=3 |issue= 3 |pages= 287–96 |year= 1999 |pmid= 10198631 |doi=10.1016/S1097-2765(00)80456-6 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Ohi N, Tokunaga A, Tsunoda H |title=A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region |journal=Cell Death Differ. |volume=6 |issue= 4 |pages= 314–25 |year= 1999 |pmid= 10381623 |doi= 10.1038/sj.cdd.4400493 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Bouillet P, Metcalf D, Huang DC |title=Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity |journal=Science |volume=286 |issue= 5445 |pages= 1735–8 |year= 1999 |pmid= 10576740 |doi=10.1126/science.286.5445.1735 |display-authors=etal}}
- {{cite journal | vauthors=Dijkers PF, Medema RH, Lammers JW |title=Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1 |journal=Curr. Biol. |volume=10 |issue= 19 |pages= 1201–4 |year= 2000 |pmid= 11050388 |doi=10.1016/S0960-9822(00)00728-4 |s2cid=17945478 |display-authors=etal|doi-access=free |bibcode=2000CBio...10.1201D }}
- {{cite journal | vauthors=Bouillet P, Zhang LC, Huang DC |title=Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim |journal=Mamm. Genome |volume=12 |issue= 2 |pages= 163–8 |year= 2001 |pmid= 11210187 |doi=10.1007/s003350010242 |s2cid=7225766 |display-authors=etal}}
- {{cite journal | vauthors=Putcha GV, Moulder KL, Golden JP |title=Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis |journal=Neuron |volume=29 |issue= 3 |pages= 615–28 |year= 2001 |pmid= 11301022 |doi=10.1016/S0896-6273(01)00238-0 |s2cid=16223140 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Murray S, Halford S, Ebenezer ND |title=Assignment of BCL2L11 to human chromosome band 2p13 with somatic cell and radiation hybrids |journal=Cytogenet. Cell Genet. |volume=92 |issue= 3–4 |pages= 353 |year= 2001 |pmid= 11435715 |doi=10.1159/000056930 |s2cid=32790948 |display-authors=etal}}
- {{cite journal | vauthors=Cheng EH, Wei MC, Weiler S |title=BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis |journal=Mol. Cell |volume=8 |issue= 3 |pages= 705–11 |year= 2001 |pmid= 11583631 |doi=10.1016/S1097-2765(01)00320-3 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Mami U, Miyashita T, Shikama Y |title=Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family |journal=FEBS Lett. |volume=509 |issue= 1 |pages= 135–41 |year= 2002 |pmid= 11734221 |doi=10.1016/S0014-5793(01)03145-3 |s2cid=82875886 |display-authors=etal|doi-access=free }}
- {{cite journal | vauthors=Bouillet P, Purton JF, Godfrey DI |title=BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes |journal=Nature |volume=415 |issue= 6874 |pages= 922–6 |year= 2002 |pmid= 11859372 |doi= 10.1038/415922a |s2cid=1404636 |display-authors=etal}}
- {{cite journal | vauthors=Marani M, Tenev T, Hancock D |title=Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis |journal=Mol. Cell. Biol. |volume=22 |issue= 11 |pages= 3577–89 |year= 2002 |pmid= 11997495 |doi=10.1128/MCB.22.11.3577-3589.2002 | pmc=133811 |display-authors=etal}}
- {{cite journal | vauthors=Liu JW, Chandra D, Tang SH |title=Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim |journal=Cancer Res. |volume=62 |issue= 10 |pages= 2976–81 |year= 2002 |pmid= 12019181 |display-authors=etal}}
- {{cite journal | vauthors=Terradillos O, Montessuit S, Huang DC, Martinou JC |title=Direct addition of BimL to mitochondria does not lead to cytochrome c release |journal=FEBS Lett. |volume=522 |issue= 1–3 |pages= 29–34 |year= 2002 |pmid= 12095614 |doi=10.1016/S0014-5793(02)02871-5 |s2cid=20419085 |doi-access=free }}
- {{cite journal | vauthors=Sugiyama T, Shimizu S, Matsuoka Y |title=Activation of mitochondrial voltage-dependent anion channel by apro-apoptotic BH3-only protein Bim |journal=Oncogene |volume=21 |issue= 32 |pages= 4944–56 |year= 2002 |pmid= 12118373 |doi= 10.1038/sj.onc.1205621 |display-authors=etal|doi-access=free }}
{{refend}}
External links
- {{UCSC genome browser|BCL2L11}}
- {{UCSC gene details|BCL2L11}}
{{gene-2-stub}}