BCL2L11

Last updated
BCL2L11
Protein BCL2L11 PDB 2K7W.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases BCL2L11 , BAM, BIM, BOD, BCL2 like 11
External IDs OMIM: 603827 MGI: 1197519 HomoloGene: 7643 GeneCards: BCL2L11
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001284410
NM_001291016
NM_009754
NM_207680
NM_207681

RefSeq (protein)
Location (UCSC) Chr 2: 111.12 – 111.17 Mb Chr 2: 127.97 – 128 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] [6]

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. [7]

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. [8]

Interactions

BCL2L11 has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Bcl-2</span> Protein found in humans

Bcl-2, encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis. It was the first apoptosis regulator identified in any organism.

<span class="mw-page-title-main">Apoptosis regulator BAX</span> Mammalian protein found in Homo sapiens

Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis.

<span class="mw-page-title-main">BH3 interacting-domain death agonist</span> Protein-coding gene in the species Homo sapiens

The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains, and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

p53 upregulated modulator of apoptosis Protein-coding gene in the species Homo sapiens

The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene. The expression of PUMA is regulated by the tumor suppressor p53. PUMA is involved in p53-dependent and -independent apoptosis induced by a variety of signals, and is regulated by transcription factors, not by post-translational modifications. After activation, PUMA interacts with antiapoptotic Bcl-2 family members, thus freeing Bax and/or Bak which are then able to signal apoptosis to the mitochondria. Following mitochondrial dysfunction, the caspase cascade is activated ultimately leading to cell death.

<span class="mw-page-title-main">Phorbol-12-myristate-13-acetate-induced protein 1</span> Protein-coding gene in the species Homo sapiens

Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the PMAIP1 gene, and is also known as Noxa.

<span class="mw-page-title-main">Bcl-2 homologous antagonist killer</span> Protein-coding gene in the species Homo sapiens

Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the BAK1 gene on chromosome 6. The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress.

<span class="mw-page-title-main">Bcl-2-associated death promoter</span>

The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family, a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis.

<span class="mw-page-title-main">Bcl-2-like protein 1</span> Protein-coding gene in the species Homo sapiens

Bcl-2-like protein 1 is a protein encoded in humans by the BCL2L1 gene. Through alternative splicing, the gene encodes both of the human proteins Bcl-xL and Bcl-xS.

<span class="mw-page-title-main">MCL1</span> Protein-coding gene in the species Homo sapiens

Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the MCL1 gene.

<span class="mw-page-title-main">BNIP3</span> Protein-coding gene in the species Homo sapiens

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein found in humans that is encoded by the BNIP3 gene.

<span class="mw-page-title-main">BCL2-related protein A1</span> Protein-coding gene in the species Homo sapiens

Bcl-2-related protein A1 is a protein in humans which is encoded by the BCL2A1 gene.

<span class="mw-page-title-main">Bcl-2-interacting killer</span> Protein-coding gene in the species Homo sapiens

Bcl-2-interacting killer is a protein that in humans is encoded by the BIK gene.

<span class="mw-page-title-main">BCL2L2</span> 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. 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.

<span class="mw-page-title-main">HRK (gene)</span>

Activator of apoptosis harakiri is a protein that in humans is encoded by the HRK gene.

<span class="mw-page-title-main">BMF (gene)</span> Protein-coding gene in the species Homo sapiens

Bcl-2-modifying factor is a protein that in humans is encoded by the BMF gene.

<span class="mw-page-title-main">BCL2L14</span> Protein-coding gene in humans

Apoptosis facilitator Bcl-2-like protein 14 is a protein that in humans is encoded by the BCL2L14 gene.

<span class="mw-page-title-main">BOK (gene)</span> Protein-coding gene in the species Homo sapiens

Bok is a protein-coding gene of the Bcl-2 family that is found in many invertebrates and vertebrates. It induces apoptosis, a special type of cell death. Currently, the precise function of Bok in this process is unknown.

<span class="mw-page-title-main">BCL2L10</span> Protein-coding gene in the species Homo sapiens

Bcl-2-like protein 10 is a protein that in humans is encoded by the BCL2L10 gene.

<span class="mw-page-title-main">DYNLL2</span> Protein-coding gene in the species Homo sapiens

Dynein light chain 2, cytoplasmic is a protein that in humans is encoded by the DYNLL2 gene.

<span class="mw-page-title-main">Bcl-2 family</span>

The Bcl-2 family consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. The Bcl-2 family proteins consists of members that either promote or inhibit apoptosis, and control apoptosis by governing mitochondrial outer membrane permeabilization (MOMP), which is a key step in the intrinsic pathway of apoptosis. A total of 25 genes in the Bcl-2 family were identified by 2008.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000153094 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027381 - 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. 1 2 3 4 5 Hsu SY, Lin P, Hsueh AJ (November 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.
  6. 1 2 3 4 O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM, Cory S, Huang DC (February 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.
  7. "Entrez Gene: BCL2L11 BCL2-like 11 (apoptosis facilitator)".
  8. Sionov RV, Vlahopoulos SA, Granot Z (2015). "Regulation of Bim in Health and Disease". Oncotarget. 6 (27): 23058–134. doi:10.18632/oncotarget.5492. PMC   4695108 . PMID   26405162.
  9. 1 2 3 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.
  10. Whitfield J, Harada K, Bardelle C, Staddon JM (November 2003). "High-throughput methods to detect dimerization of Bcl-2 family proteins". Anal. Biochem. 322 (2): 170–8. doi:10.1016/j.ab.2003.07.014. PMID   14596824.
  11. Day CL, Puthalakath H, Skea G, Strasser A, Barsukov I, Lian LY, Huang DC, Hinds MG (February 2004). "Localization of dynein light chains 1 and 2 and their pro-apoptotic ligands". Biochem. J. 377 (Pt 3): 597–605. doi:10.1042/BJ20031251. PMC   1223895 . PMID   14561217.
  12. Vadlamudi RK, Bagheri-Yarmand R, Yang Z, Balasenthil S, Nguyen D, Sahin AA, den Hollander P, Kumar R (June 2004). "Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes". Cancer Cell. 5 (6): 575–85. doi: 10.1016/j.ccr.2004.05.022 . PMID   15193260.
  13. Bae J, Leo CP, Hsu SY, Hsueh AJ (August 2000). "MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain". J. Biol. Chem. 275 (33): 25255–61. doi: 10.1074/jbc.M909826199 . PMID   10837489.
  14. Heckmeier PJ, Ruf J, Buhrke D, Janković BG, Hamm P (September 2022). "Signal Propagation Within the MCL-1/BIM Protein Complex". Journal of Molecular Biology. 434 (17): 167499. doi: 10.1016/j.jmb.2022.167499 . PMID   35189130.

Further reading