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FLASH GENE
Symbol BCL2L11 contributors: mct/npt/pgu - updated : 05-03-2017
HGNC name BCL2-like 11 (apoptosis facilitator)
HGNC id 994
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • short BH3 domain required for BCL-2 binding and cytotoxicity
  • a dynein binding domain (DBD), with a putative phosphorylation sites, playing a role for the anti-proapoptotic activity of GRB10
  • a hydrophobic C-terminus
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to rattus Bim
    homolog to murine Bcl2l11
    Homologene
    FAMILY
  • BH3-only family
  • Bcl-2 superfamily
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • localized to intracytoplasmic membranes
  • sequestered to the microtubule-associated dynein motor complex
  • primarily localized to mitochondrial and cytoskeleton-associated fractions (pMID: 23152504)
  • basic FUNCTION
  • regulator of cell death that operate at the mitochondrial membrane to control caspase activation,
  • involved in certain apoptotic responses and to prevent overproduction of hematopoietic cells
  • playing a role in neuronal and lymphocyte apoptosis
  • functionning as an essential initiator of the apoptosis in thymocyte-negative selection
  • involved in cytokine-dependent survival pathways
  • potent activator of apoptosis and, in neurons, induces the direct activation of BAX
  • with PMAIP1, establish a connection between FKHRL1 and mitochondria, and both BH3-only proteins are critically involved in FKHRL1-induced apoptosis in neuroblastoma
  • transcriptionally and/or post-translationally induced in response to diverse apoptotic stimuli, such as cytokine deprivation or deregulated calcium flux, in a broad range of hematopoeitic, epithelial, and neuronal cell types
  • mediates motoneuron loss in a model of amyotrophic lateral sclerosis
  • implicated in the regulation of cell death induction in multiple cell types and tissues in response to a large number of stimuli, including growth factor or cytokine deprivation, calcium flux, ligation of antigen receptors on T and B cells, glucocorticoid or loss of adhesion
  • playing an important role in eliminating activated T cells even when IL2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis
  • critical sensor and mediator in the mitochondrial-dependent apoptosis
  • with BAX are required for GNB2L1-mediated mitochondrial cell death
  • proapoptotic member of the BCL2 family and is primarily involved in the regulation of the intrinsic apoptotic pathway
  • essential for the initiation of several pathways that induce apoptosis in thymocytes, including cytokine withdrawal and calcium flux
  • essential for thymocyte apoptosis caused by strong TCR stimulation and critical for negative selection of autoreactive thymocytes
  • its expression may be responsible for the inherent sensitivity of the developing retinal vasculature to changes in oxygen levels, and promotes vessel obliteration in response to hyperoxia
  • apoptosis regulated by BCL2L11- and PMAIP1-driven loss of MCL1 is thus the final step in neutrophil differentiation, required for the termination of neutrophil function and neutrophil-dependent inflammation
  • for optimal tumor suppressive activity, must be able to interact with all and not just select pro-survival BCL2 family members
  • has a major role in hematopoietic homeostasis, particularly in the lymphocyte compartment, where it strongly affects immune function
  • inhibits autophagy by recruiting Beclin 1 to microtubules
  • in response to toxic stimuli, is released from its interaction with DYNLL1 and can induce apoptosis by inactivating anti-apoptotic BCL2 proteins and by activating BAX-BAK1
  • having a dual effects in inhibiting autophagy and promoting apoptosis and may have important roles in disease pathogenesis
  • plays a physiological role in promoting cell survival in addition to its well known function in apoptosis induction
  • BCL2L11 and BBC3 can directly activate the proapoptotic proteins BAX and BAK1 to permeabilize mitochondria, leading to caspase activation and apoptosis
  • BCL2L11 and BBC3 are the sentinels that interconnect kinase signaling networks and the mitochondrion-dependent apoptotic program, which offers therapeutic insights for designing novel cell death mechanism-based anticancer strategies
  • is required for cell death mediated by antimitotic agents
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    text apoptotic activator
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimers with a number of antiapoptotic bcl-2 protein including MCL-1, BCL-2, BCL-XL, BFL-1 and BHRF1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to BCL2, BCL2L1/BCL-X(L), MCL1, BFL1, BHRF-1, LC8 cytoplasmic dynein light chain
  • 17beta-estradiol (E2) upregulates expression of antiapoptotic BCL2L2 and downregulates expression of proapoptotic BCL2L11 in an estrogen receptor (ER)-dependent manner
  • coordinated action of MCL1, IER3, and BCL2L11 controls cell death and survival (new regulatory circuit)
  • GRB10 interacted with the DBD (dynein binding domain) of BCl2L11 and inhibited apoptosis triggered by overexpression of DBD containing BCL2L11 isoforms
  • BID, BCL2L11, and BBC3 are required to activate BAX- and BAK1-dependent mitochondrial apoptosis
  • PMAIP1 is strongly upregulated and became associated with both MCL1 and BCL2L11 during apoptosis induced by proteasome inhibition
  • PRKAR1A is an interacting partner of BCL2L11
  • TRIM2 binds to BCL2L11 when it is phosphorylated by p42/p44 MAPK
  • CCNB1 interacts with the BH3-only protein BCl2L11 and mediates its phosphorylation by CDK1 during mitosis
  • CDH2 engagement mediates neuronal cell survival by enhancing the MAP kinase pathway and down-regulating the pro-apoptotic protein BCL2L11
  • BBC3 cooperates with BCL2L11 to impose a thymic-deletion checkpoint to peripheral self-antigens and cement the notion that defects in apoptosis alone are sufficient to cause autoimmune disease
  • interacts with BECN1, and this interaction is facilitated by DYNLL1 (BCL2L11 recruits BECN1 to microtubules by bridging BECN1 and DYNLL1, thereby inhibiting autophagy)
  • E2F1 binds to the BCL2L11 promoter at multiple sites
  • BBC3 like BCL2L11, PMAIP1, is able to act as a direct BAK1 activator
  • IL4 was able to inhibit BCL2L11 upregulation and prevent cell death
  • BCL2L11 and PMAIP1 are mitochondrial effectors of TAF6delta-driven apoptosis
  • SPZ1 reduces apoptosis by altering the stability of BCL2L11
  • cell & other
  • intracytoplasmic membrane
  • REGULATION
    activated by by overexpression of TARDBP
    induced by the forkhead transcription factor FKHR-L1 and nerve growth factor (NGF)
    inhibited by MCL1
    Other regulated both in the transcript and post transcript process
    regulated by the ERK1/2 survival pathway (MAPK1 and MAPK3)
    hypoxic conditions inhibit anoikis and block expression of proapoptotic BCL2L11 and BMF in epithelial cells

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