Affinage

BCL2L1

Bcl-2-like protein 1 · UniProt Q07817

Length
233 aa
Mass
26.0 kDa
Annotated
2026-06-09
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCL2L1 is a central rheostat of the intrinsic apoptotic pathway whose pre-mRNA is alternatively spliced into the anti-apoptotic Bcl-xL and the pro-apoptotic Bcl-xS isoforms, which functionally oppose one another (PMID:8358789). Bcl-xL restrains mitochondrial outer membrane permeabilization through several converging mechanisms: it forms stable heterodimers with Bax to raise the apoptotic threshold (PMID:8626425), directly binds and physiologically restrains Bak through interactions essential for T-cell and platelet survival in vivo (PMID:27198225), retrotranslocates Bax from mitochondria back to the cytosol in healthy cells (PMID:21458670), and competes with Bax for membrane recruitment by sequestering tBid and activated Bax in nonproductive complexes without oligomerizing, acting as a dominant-negative Bax (PMID:18547146, PMID:19820711). Beyond protein–protein restraint, Bcl-xL inserts into membranes to form pH-sensitive, cation-selective ion channels (PMID:9002522) and binds ceramide via its hydrophobic groove to block ceramide channel formation (PMID:26215742); structural work shows its C-terminus toggles between a surface groove in the soluble state and a transmembrane configuration upon membrane integration (PMID:25731750). Bcl-xL activity is set post-translationally—Mst1 phosphorylation at Ser14 in the BH4 domain antagonizes Bax binding and licenses apoptosis (PMID:24813943), while caspase cleavage of its loop domain converts Bcl-xL into a pro-apoptotic fragment (PMID:9435230)—and is opposed by the BH3-only protein Noxa, which neutralizes Bcl-xL and targets it for proteasomal degradation (PMID:20051518, PMID:33982799). The protective Bcl-xL isoform is essential for survival of dendritic cells (PMID:15383573) and supports neuronal outgrowth and survival (PMID:24787232), and it also discharges apoptosis-independent roles: suppressing FUNDC1-mediated mitophagy by inhibiting the PGAM5 phosphatase (PMID:25126723), suppressing autophagy by binding Beclin1 to displace PIK3C3 (PMID:33664238), promoting mitochondrial fission/fusion and biomass in neurons (PMID:19255249), and engaging active RAS through its BH4 domain to sustain cancer stem cell signaling (PMID:29066722). The Bcl-xL/Bcl-xS ratio is itself heavily regulated at the RNA level: Sam68 (modulated by Fyn phosphorylation and hnRNP A1) (PMID:17371836), PKC signaling acting on a cis exonic element (PMID:17923691), PRMT2 (PMID:28057797), SRSF1 (PMID:33664238), and RNA G-quadruplexes near the competing 5' splice sites—read by RBM25 and tunable by G4 ligands—collectively determine isoform choice (PMID:29156002, PMID:37811881), while transcription is driven by Bcr/Abl–STAT5 (PMID:10979976) and mRNA stability by nucleolin binding the 3'-UTR (PMID:18281479).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Established that a single gene encodes two functionally opposing apoptotic regulators, defining BCL2L1 as a splicing-controlled switch rather than a single anti-apoptotic factor.

    Evidence Molecular cloning and stable transfection of IL-3-dependent cells with survival assays after growth factor withdrawal

    PMID:8358789

    Open questions at the time
    • Mechanism by which Bcl-xS antagonizes survival not resolved
    • Splicing regulators unknown at this stage
  2. 1996 High

    Showed Bcl-xL acts in part by direct heterodimerization with Bax, providing a biochemical basis for raising the apoptotic threshold.

    Evidence In vitro binding and reciprocal co-IP from mammalian cells with dose-dependent survival assays

    PMID:8626425

    Open questions at the time
    • Whether Bax sequestration is the dominant in vivo mechanism unaddressed
    • Bcl-xS mechanism remained distinct and undefined
  3. 1997 High

    Demonstrated Bcl-xL is itself a membrane pore-former, suggesting a channel activity intrinsic to its function beyond protein binding.

    Evidence Planar lipid bilayer electrophysiology and synthetic vesicle reconstitution

    PMID:9002522

    Open questions at the time
    • Physiological substrate/ion of the channel in cells not established
    • Relationship of channel activity to apoptosis control unclear
  4. 1998 High

    Revealed that caspase cleavage converts the protective Bcl-xL into a lethal fragment, establishing a feed-forward proteolytic switch during apoptosis.

    Evidence In vitro caspase cleavage, site-directed mutagenesis, and cell death assays

    PMID:9435230

    Open questions at the time
    • In vivo contribution of the cleavage fragment to physiological death unquantified
    • Structural basis of the pro-apoptotic fragment unknown
  5. 2000 High

    Identified Bcr/Abl–STAT5 as a transcriptional driver of BCL-X, linking oncogenic signaling to Bcl-xL-mediated survival.

    Evidence Inducible expression, BCL-X promoter/luciferase reporter, and dominant-negative STAT5 epistasis

    PMID:10979976

    Open questions at the time
    • Direct STAT5 binding to the promoter not mapped
    • Effect on isoform ratio versus total expression not separated
  6. 2007 High

    Defined RNA-level control of isoform choice via Sam68 and showed kinase signaling (Fyn, PKC) and a cis exonic element steer splicing toward Bcl-xL or Bcl-xS.

    Evidence RNAi, overexpression, co-IP, kinase epistasis, and minigene splicing assays with cis-element transplantation

    PMID:17371836 PMID:17923691

    Open questions at the time
    • Direct splice-site mechanism of Sam68/PKC integration unresolved
    • PKC findings are Medium-confidence single-lab
  7. 2008 High

    Reconstituted MOMP inhibition with recombinant proteins, establishing that Bcl-xL functions as a dominant-negative Bax by sequestering both tBid and activated Bax without oligomerizing.

    Evidence In vitro liposome and isolated-mitochondria permeabilization with full-length recombinant proteins and interaction-abolishing mutants

    PMID:18547146

    Open questions at the time
    • Relative weighting of tBid versus Bax sequestration in cells not fixed
    • Membrane context of these interactions only partly captured
  8. 2009 Medium

    Showed Bcl-xL has apoptosis-independent effects on mitochondrial dynamics, increasing fission, fusion, and biomass in neurons.

    Evidence Live fluorescence imaging with computational fission/fusion analysis after Bcl-xL overexpression in neurons

    PMID:19255249

    Open questions at the time
    • Overexpression-based; loss-of-function effect on dynamics untested here
    • Molecular effector linking Bcl-xL to fission/fusion machinery unknown
  9. 2009 High

    Quantified that the membrane environment, not solution conditions, governs tBid–Bcl-xL binding and that only active tBid engages Bcl-xL.

    Evidence Fluorescence correlation spectroscopy in solution and lipid bilayers with BH3 peptide competition

    PMID:19820711

    Open questions at the time
    • Structural basis of the distinct membrane-bound complex unresolved
    • Generality to other BH3 ligands not tested
  10. 2011 High

    Established retrotranslocation of Bax from mitochondria to cytosol as a continuous, Bcl-xL-dependent surveillance mechanism in healthy cells.

    Evidence FLIP live-cell imaging with conformation-locking Bax disulfide mutants, cell-free MOMP, and co-IP

    PMID:21458670

    Open questions at the time
    • Energetics and directionality determinants of retrotranslocation incompletely defined
    • How signaling tips retrotranslocation toward MOMP not resolved
  11. 2014 High

    Connected post-translational control and non-apoptotic function: Mst1 Ser14 phosphorylation disarms Bcl-xL–Bax restraint, while Bcl-xL inhibits PGAM5 to suppress FUNDC1-mediated mitophagy.

    Evidence In vitro kinase assay, Ser14 mutagenesis, co-IP, fractionation, and mitophagy quantification with BCL2 isoform controls

    PMID:24813943 PMID:25126723

    Open questions at the time
    • In vivo significance of Ser14 phosphorylation outside cardiac myocytes unclear
    • Structural basis of Bcl-xL–PGAM5 inhibition unmapped
  12. 2015 High

    Expanded Bcl-xL membrane biology: it binds ceramide to block ceramide channels, and structural work defined how its C-terminus repartitions between groove and bilayer without altering the soluble fold.

    Evidence Hydrophobic-groove mutagenesis with planar-membrane ceramide channel assays and NMR of full-length protein in soluble and membrane states

    PMID:25731750 PMID:26215742

    Open questions at the time
    • Physiological frequency of ceramide-channel inhibition versus Bax regulation unquantified
    • Functional state of the membrane-inserted C-terminus in apoptosis control unresolved
  13. 2016 High

    Demonstrated in vivo that Bcl-xL restraint of Bak (not only Bax) is essential, using a binding-selective Bak mutant that compromises T-cell and platelet survival.

    Evidence Crystal structure of Bak mutant, SPR binding, and Bak knock-in mouse genetics with survival assays

    PMID:27198225

    Open questions at the time
    • Tissue-specific dependence on Bak versus Bax restraint not fully mapped
    • Interplay with other pro-survival relatives in vivo unaddressed
  14. 2017 Medium

    Extended Bcl-xL into oncogenic signaling, showing a BH4-dependent interaction with active RAS that sustains stemness independent of apoptotic pressure, and added PRMT2 as a splicing-ratio regulator.

    Evidence Co-IP with BH4 domain mutants and stemness assays; PRMT2–SAM68 SH3 pull-down with splicing readout

    PMID:28057797 PMID:29066722

    Open questions at the time
    • RAS interaction shown by co-IP without reciprocal structural validation
    • Direct versus indirect role of PRMT2 on splice-site selection unresolved
  15. 2018 Medium

    Identified RNA G-quadruplexes near both alternative 5' splice sites as druggable structural determinants of Bcl-xL/Bcl-xS choice.

    Evidence G4-ligand panel with minigene and endogenous splicing RT-PCR plus apoptosis assays

    PMID:29156002

    Open questions at the time
    • Endogenous proteins reading the G4s not identified in this study
    • Single-lab functional ligand data
  16. 2021 Medium

    Linked SRSF1-driven Bcl-xL production to autophagy suppression via Beclin1–PIK3C3 dissociation, and showed NOXA-driven proteasomal degradation of Bcl-xL during chemotherapy.

    Evidence Splicing RT-PCR with Beclin1/PIK3C3 co-IPs and LC3-II assays; NOXA co-IP with proteasome-inhibitor rescue and pathway epistasis

    PMID:33664238 PMID:33982799

    Open questions at the time
    • Direct versus splicing-mediated contribution of SRSF1 to autophagy not fully separated
    • E3 ligase mediating NOXA-driven degradation not identified
  17. 2023 High

    Identified RBM25 as the direct G-quadruplex reader (via its RE motif) that promotes Bcl-xS production, providing a protein basis for G4-ligand-tunable splicing.

    Evidence In vitro RNA pull-down, EMSA, RBM25 domain mutagenesis, G4-ligand competition, and splicing/apoptosis assays

    PMID:37811881

    Open questions at the time
    • Interplay of RBM25 with other splicing factors at the locus unresolved
    • Structural model of the RBM25–rG4 complex not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many layers of regulation—transcription, mRNA stability, splice-isoform choice, post-translational modification, and degradation—are integrated to set the Bcl-xL/Bcl-xS balance in a given cell context remains unresolved.
  • No unified quantitative model linking splicing regulators to apoptotic outcome
  • Context-specific weighting of apoptotic versus non-apoptotic Bcl-xL functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140313 molecular sequestering activity 4 GO:0098772 molecular function regulator activity 2 GO:0005215 transporter activity 1 GO:0008289 lipid binding 1
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9612973 Autophagy 2
Partners
BAK1BAXBECN1BIDHRASPGAM5PMAIP1SAM68

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 BCL2L1 encodes two alternatively spliced isoforms: Bcl-xL (anti-apoptotic) and Bcl-xS (pro-apoptotic). Bcl-xL stably transfected into an IL-3-dependent cell line inhibits apoptosis upon growth factor withdrawal at least as well as Bcl-2, while Bcl-xS inhibits the protective effect of Bcl-2. Stable transfection of IL-3-dependent cell lines; cell survival assays after growth factor withdrawal; molecular cloning and alternative splicing analysis Cell High 8358789
1996 Bcl-xL forms stable complexes with Bax both in vitro and in vivo (co-immunoprecipitation), increasing the apoptotic threshold in a dose-dependent manner. Bcl-xS does not form observable heterodimers with other Bcl-2 family members by co-immunoprecipitation from mammalian cells, suggesting it acts by a distinct mechanism rather than by competing for Bax binding. In vitro binding assays; co-immunoprecipitation from mammalian cells; dose-dependent cell survival assays The Journal of biological chemistry High 8626425
1997 Bcl-xL inserts into synthetic lipid vesicles or planar lipid bilayers and forms pH-sensitive, cation-selective ion-conducting channels with multiple conductance states, similar to pore-forming bacterial toxins. Planar lipid bilayer electrophysiology; synthetic lipid vesicle reconstitution; ion channel recordings Nature High 9002522
1998 The loop domain of Bcl-xL is cleaved by caspases in vitro and in cells undergoing apoptosis. Mutation of the caspase cleavage site combined with a BH1 domain mutation impairs death-inhibitory activity. Once cleaved, the C-terminal fragment of Bcl-xL potently induces apoptosis, converting Bcl-xL from protective to lethal. In vitro caspase cleavage assay; site-directed mutagenesis; cell death assays after Sindbis virus infection or IL-3 withdrawal Proceedings of the National Academy of Sciences of the United States of America High 9435230
2000 Bcr/Abl activates transcription of the BCL-X gene through STAT5. Constitutively active STAT5-1*6 induces Bcl-xL expression and promotes survival. A dominant-negative STAT5 mutant blocks both Bcr/Abl-induced BCL-X promoter activity and Bcl-xL protein increase. Tetracycline-inducible expression system; BCL-X promoter/luciferase reporter assays; dominant-negative STAT5 expression; Western blotting Blood High 10979976
2007 The RNA-binding protein Sam68 binds BCL-x mRNA and modulates its alternative splicing: Sam68 depletion increases anti-apoptotic Bcl-xL, while its overexpression increases pro-apoptotic Bcl-xS. Tyrosine phosphorylation of Sam68 by Fyn kinase inverts this effect, favoring Bcl-xL splice site selection. Sam68 interacts with hnRNP A1, and hnRNP A1 depletion or mutations impairing this interaction attenuate Bcl-xS splicing. RNA interference; overexpression; co-immunoprecipitation; minigene splicing assays; point mutation analysis of RNA-binding domain The Journal of cell biology High 17371836
2007 PKC inhibition (including staurosporine and more specific PKC inhibitors) shifts BCL-x pre-mRNA splicing toward the pro-apoptotic Bcl-xS isoform. This requires active transcription but no new protein synthesis and is independent of caspase activation. An exonic region upstream of the Bcl-xS 5' splice site mediates the staurosporine-dependent splicing shift when transplanted into other alternative splicing units. PKC inhibitor treatment; minigene splicing assays with deletion and transplant constructs; actinomycin D and caspase inhibitor controls; RT-PCR isoform analysis Molecular and cellular biology Medium 17923691
2008 Bcl-xL inhibits mitochondrial outer membrane permeabilization (MOMP) by competing with Bax for activation by tBid. Using full-length recombinant proteins and liposome/mitochondria permeabilization assays, tBid recruits both Bcl-xL and Bax to membranes. Mutagenesis shows both Bcl-xL–tBid and Bcl-xL–Bax interactions contribute to anti-apoptotic function. Bcl-xL sequesters tBid and Bax in nonproductive interactions without forming oligomers, functioning as a dominant-negative Bax. In vitro liposome permeabilization assay; isolated mitochondria MOMP assay; full-length recombinant protein reconstitution; site-directed mutagenesis abolishing specific interactions PLoS biology High 18547146
2009 Membrane strongly promotes binding between tBid and Bcl-xL (truncated at C-terminus). Only the active form tBid (not full-length BID) binds Bcl-xL. A BH3 peptide from BID disrupts the tBid-Bcl-xL complex in solution but only partially in lipid bilayers, indicating that tBid–Bcl-xL interactions in membrane are distinct from those in solution. Fluorescence correlation spectroscopy (FCS) in solution and in lipid bilayers; BH3 peptide competition assay Nature structural & molecular biology High 19820711
2009 Bcl-xL increases the rates of both mitochondrial fission and fusion in neurons, and importantly increases mitochondrial biomass, resulting in longer organelle morphology. These effects are measured in neuronal processes using fluorescence microscopy and computational analysis. Fluorescence microscopy with computational fission/fusion frequency measurement; overexpression of Bcl-xL in cultured neurons The Journal of cell biology Medium 19255249
2011 Bcl-xL retrotranslocates Bax from the mitochondria back into the cytosol in healthy cells. FLIP (fluorescence loss in photobleaching) reveals constant retrotranslocation of wild-type Bax but not intramolecular disulfide-tethered Bax (which is locked in its cytosolic conformation and accumulates on mitochondria). Bcl-xL retrotranslocation activity depends on pro-survival Bcl-2 family proteins. Intramolecular disulfide tethering to constrain Bax conformation; fluorescence loss in photobleaching (FLIP); cell-free MOMP assay; detergent co-immunoprecipitation Cell High 21458670
2014 BCL2L1/Bcl-xL (but not BCL2) suppresses FUNDC1-mediated mitophagy under hypoxia through its BH3 domain. Mechanistically, Bcl-xL interacts with and inhibits the mitochondrial phosphatase PGAM5, preventing dephosphorylation of FUNDC1 at Ser13, which is required for mitophagy activation. Co-immunoprecipitation of Bcl-xL and PGAM5; phosphorylation assays of FUNDC1 Ser13; BCL2 vs BCL2L1 comparison; BH3 domain requirement; mitophagy quantification Autophagy High 25126723
2014 Mst1 phosphorylates Bcl-xL at Ser14 within the BH4 domain, antagonizing Bcl-xL–Bax binding. This activates Bax and triggers mitochondria-mediated apoptosis in cardiac myocytes. Mst1 activation is localized to mitochondria via a K-Ras–RASSF1A–Mst1 signaling cassette in response to oxidative stress. In vitro kinase assay; site-directed mutagenesis of Ser14; co-immunoprecipitation of Bcl-xL and Bax; mitochondrial fractionation; cardiac myocyte apoptosis assays Molecular cell High 24813943
2015 Bcl-xL physically interacts with ceramide via the hydrophobic groove, and this interaction inhibits ceramide channel formation in mitochondrial outer membranes. Bcl-xL point mutations that specifically weaken ceramide binding reduce the ability of Bcl-xL to inhibit ceramide channel formation and protect cells from apoptosis in a stimulus-dependent manner, distinct from but overlapping with Bax channel regulation. Site-directed mutagenesis of Bcl-xL hydrophobic groove; planar lipid membrane ceramide channel assay; fluorescently-labeled ceramide binding; stable expression of mutants in Bcl-xL-deficient cells; apoptosis assays Biochimica et biophysica acta High 26215742
2015 Bcl-xL conformation upon membrane integration: the C-terminus interacts with a conserved surface groove in the water-soluble state and inserts across the phospholipid bilayer in the membrane-bound state. Contrary to current models, membrane binding does not induce a conformational change in the soluble domain; both states bind a known ligand with affinities modulated by the protein state. NMR spectroscopy of full-length Bcl-xL in detergent-free environments; lipid bilayer reconstitution; ligand binding affinity measurements Journal of molecular biology High 25731750
2016 Physiological restraint of Bak by Bcl-xL is essential for cell survival in vivo. A Bak mutation (E75L in mouse, Q77L in human) specifically disrupts interaction with Bcl-xL without affecting Bak structure or killing activity. Loss of Bcl-xL binding to Bak causes increased apoptotic sensitivity in vitro and significant defects in T-cell and blood platelet survival in vivo. Crystal structure of Bak mutant; surface plasmon resonance binding measurements; mouse genetics (Bak knock-in); T-cell and platelet survival assays Genes & development High 27198225
2017 BCL-xL directly interacts with constitutively active RAS in a BH4 domain-dependent manner. This interaction favors full activation of RAS downstream signaling, leading to RAS-induced expression of stemness regulators and maintenance of cancer initiating cell phenotype, independent of apoptotic pressure. Co-immunoprecipitation of BCL-xL and RAS; BH4 domain mutants; comparative proteomics; functional stemness assays Nature communications Medium 29066722
2017 PRMT2 interacts with the splicing factor SAM68 via its SH3 domain and regulates SAM68 subcellular localization. PRMT2 expression promotes an increase in the BCL-xL/BCL-xS splicing ratio in TNF-α or LPS-stimulated cells, linking PRMT2 to BCL-x alternative splicing regulation. Proteomics (SH3 domain pull-down); co-immunoprecipitation of PRMT2 and SAM68; subcellular localization analysis; RT-PCR splicing isoform quantification Journal of biochemistry Medium 28057797
2018 RNA G-quadruplexes (G4s) form in BCL-x pre-mRNA near each of the two alternative 5' splice sites. G4-stabilizing ligands (including ellipticine GQC-05) shift BCL-x splicing, antagonizing the major 5' splice site leading to Bcl-xL and activating the alternative splice site leading to pro-apoptotic Bcl-xS. Ligands act independently at the two splice sites. G4 ligand panel treatment; minigene splicing assays; endogenous splicing RT-PCR; apoptosis assays; structure-activity relationship analysis of G4 ligands Nucleic acids research Medium 29156002
2021 SRSF1 promotes splicing of the long anti-apoptotic Bcl-xL isoform, which then interacts with Beclin1 to dissociate the Beclin1-PIK3C3 complex, thereby suppressing autophagosome formation. SRSF1 also directly interacts with PIK3C3 to disrupt Beclin1-PIK3C3 interaction. Splicing assays (RT-PCR); co-immunoprecipitation of Bcl-xL and Beclin1; co-immunoprecipitation of SRSF1 and PIK3C3; LC3-II accumulation assays; siRNA knockdown Signal transduction and targeted therapy Medium 33664238
2023 RBM25 directly and specifically binds to GQ-2, an RNA G-quadruplex in BCL-x pre-mRNA near the alternative 5' splice site leading to Bcl-xS. This RBM25–rG4 interaction requires the RE (arginine-glutamate-rich) motif of RBM25 and is crucial for Bcl-xS production. G4 ligands (PhenDC3, PhenDH8, PhenDH9) enhance RBM25 binding to GQ-2 rG4, promoting Bcl-xS expression and apoptosis. In vitro RNA pull-down; EMSA; G4 ligand binding assays; RBM25 domain mutagenesis; minigene and endogenous splicing assays; apoptosis assays; G4 ligand screen of 90 compounds Nucleic acids research High 37811881
2004 FAST (Fas-activated serine/threonine phosphoprotein) localizes to mitochondria and interacts with BCL-xL at the mitochondrial membrane. The BCL-xL binding domain of FAST maps to a BH3-related domain distinct from the mitochondrial-tethering domain (MTD). Both domains are required for FAST–BCL-xL interaction, but the MTD requirement can be satisfied by a heterologous MTD. Immunofluorescence microscopy; subcellular fractionation; co-immunoprecipitation; domain deletion/transplant experiments Biochemical and biophysical research communications Medium 15110758
2003 Bcl-xS expressed in Xenopus oocytes localizes predominantly to mitochondria and induces caspase-dependent cytochrome c release that requires the BH3 domain. This apoptotic effect is inhibited by co-expression of Bcl-2 or Bcl-xL. The transmembrane domain and BH3 domain of Bcl-xS are both required for apoptotic effect. Xenopus oocyte expression system; subcellular fractionation; cytochrome c release assay; caspase inhibitor treatment; BH3 and transmembrane domain mutagenesis Molecular cancer research Medium 12556558
2008 Nucleolin binds specifically to AU-rich elements (AUUUA) in the 3'-UTR of BCL-xL mRNA and stabilizes it. Nucleolin overexpression stabilizes BCL-xL mRNA in cells, while nucleolin siRNA knockdown shortens BCL-xL mRNA half-life. The stabilizing effect depends on the poly(A) tail and involves nucleolin–poly(A)-binding protein interaction via RGG motifs. RNA affinity capture with synthetic Bcl-xL 3'-UTR; mass spectrometry identification; RIP (RNA immunoprecipitation); siRNA knockdown; mRNA half-life measurements; overexpression Cancer research Medium 18281479
2019 BMPRII deficiency modulates alternative splicing of BCL-x transcripts in a cell-type-specific manner: promoting Bcl-xL in PASMCs while inhibiting it in endothelial cells. This pro-survival effect is mediated through ALK1 but not ALK3. BMPRII physically interacts with ALK1, and pathogenic mutations in BMPR2 abolish this interaction. Co-immunoprecipitation of BMPRII and ALK1; RT-PCR splicing isoform analysis; cell-type-specific knockdown; apoptosis assays; analysis of PAH patient cells and lungs Human molecular genetics Medium 30809644
2021 NOXA upregulation leads to proteasomal degradation of BCL2L1 (Bcl-xL) in daunorubicin-treated AML cells, through the NOX4-ROS-p38 MAPK-GSK3β-CREB signaling axis. Restoration of BCL2L1 expression alleviates daunorubicin-induced mitochondrial depolarization and cell death. NOXA associates with both Bcl-xL and MCL1 by immunoprecipitation. Immunoprecipitation; proteasome inhibitor rescue experiments; siRNA knockdown of pathway components; Western blotting; mitochondrial membrane potential assays Journal of cellular physiology Medium 33982799
2006 BCL-xL is required for dendritic cell survival in vivo. Conditional deletion of bcl-x in skin-residing dendritic cells causes rapid apoptotic disappearance from draining lymph nodes and failure to mount effective immune responses. Trans-complementation with BCL-xL rescues DC survival, and RNAi silencing of the Bcl-xL isoform (but not Bcl-xS) specifically recapitulates the survival defect. Cre-loxP conditional gene deletion in DCs; gene gun DNA vaccine immunization; RNA interference isoform-specific silencing; trans-complementation with Bcl-xL Journal of immunology High 15383573
2010 Noxa co-immunoprecipitates with endogenous Bcl-xL in neuroblastoma cells (in addition to MCL1), and this association functionally neutralizes Bcl-xL. Retroviral expression of Bcl-xL (but not MCL1) prevents bortezomib-induced apoptosis, and Noxa knockdown reduces cell death, establishing that Noxa-mediated neutralization of Bcl-xL is required for bortezomib-induced apoptosis. Co-immunoprecipitation; shRNA knockdown; retroviral overexpression; apoptosis assays The Journal of biological chemistry Medium 20051518
2015 Bcl-xL depletion in hippocampal neurons impairs neurite outgrowth followed by delayed cell death dependent on upregulation of death receptor 6 (DR6). DR6 depletion partially rescues neuronal process loss, placing DR6 downstream of Bcl-xL in the regulation of neuronal outgrowth. Under hypoxia, Bcl-xL-depleted neurons show increased DR6, neuronal process loss, and death. shRNA depletion of Bcl-xL and DR6; neurite outgrowth measurement; hypoxia model; epistasis by DR6 rescue of Bcl-xL depletion phenotype Antioxidants & redox signaling Medium 24787232

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 2985 8358789
1997 Bcl-x(L) forms an ion channel in synthetic lipid membranes. Nature 687 9002522
2011 Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell 506 21458670
1998 Modulation of cell death by Bcl-XL through caspase interaction. Proceedings of the National Academy of Sciences of the United States of America 449 9435230
1995 Expression of bcl-xL can confer a multidrug resistance phenotype. Blood 371 7655019
2007 The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x. The Journal of cell biology 270 17371836
2008 Bcl-XL inhibits membrane permeabilization by competing with Bax. PLoS biology 252 18547146
2001 Expression and role of Bcl-xL in human hepatocellular carcinomas. Hepatology (Baltimore, Md.) 228 11431734
2000 Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood 217 10979976
1998 Bcl-xL is an antiapoptotic regulator for postnatal CNS neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 214 9437022
1995 Bclx regulates the survival of double-positive thymocytes. Proceedings of the National Academy of Sciences of the United States of America 212 7761398
2000 Regulation of Bcl-xL: a little bit of this and a little bit of STAT. Current opinion in oncology 199 11085453
1996 Bcl-x(S) anatagonizes the protective effects of Bcl-x(L). The Journal of biological chemistry 187 8626425
2009 Bcl-x L increases mitochondrial fission, fusion, and biomass in neurons. The Journal of cell biology 184 19255249
1998 Expression of Bcl-x in erythroid precursors from patients with polycythemia vera. The New England journal of medicine 178 9475763
1999 Induction of endogenous Bcl-xS through the control of Bcl-x pre-mRNA splicing by antisense oligonucleotides. Nature biotechnology 171 10545916
1994 Bcl-2 and Bcl-x: regulatory switches for lymphoid death and survival. Immunology today 160 7848520
2014 The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy. Autophagy 156 25126723
1999 Immunohistochemical analysis of Bcl-2, Bax, Bcl-X, and Mcl-1 expression in pancreatic cancers. Oncology 142 9885381
1997 The roles of Bcl-X(L) and apopain in the control of erythropoiesis by erythropoietin. Blood 136 9226163
2014 Mst1 promotes cardiac myocyte apoptosis through phosphorylation and inhibition of Bcl-xL. Molecular cell 124 24813943
2001 Transcriptional regulation of the bcl-x gene encoding the anti-apoptotic Bcl-xL protein by Ets, Rel/NFkappaB, STAT and AP1 transcription factor families. Histology and histopathology 116 11332715
2009 Membrane promotes tBID interaction with BCL(XL). Nature structural & molecular biology 107 19820711
2019 Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing. Frontiers in genetics 102 31552099
2021 SRSF1 inhibits autophagy through regulating Bcl-x splicing and interacting with PIK3C3 in lung cancer. Signal transduction and targeted therapy 98 33664238
1995 Primitive human hematopoietic precursors express Bcl-x but not Bcl-2. Blood 97 7542499
1998 bcl-2, bax, bcl-XL, and bcl-XS expression in normal and neoplastic ovarian tissues. Clinical cancer research : an official journal of the American Association for Cancer Research 91 9516944
1996 Bcl-x rather than Bcl-2 mediates CD40-dependent centrocyte survival in the germinal center. Blood 86 8695854
1997 A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity 84 9390687
2016 Bcl-xL is an oncogenic driver in colorectal cancer. Cell death & disease 83 27537525
1995 Function and expression of the Bcl-x gene in the developing and adult nervous system. Neuroreport 83 8547598
2008 Inhibition of the Bcl-xL deamidation pathway in myeloproliferative disorders. The New England journal of medicine 79 19109573
2019 Bcl-XL: A multifunctional anti-apoptotic protein. Pharmacological research 70 31734345
2013 Functions of BCL-X L at the Interface between Cell Death and Metabolism. International journal of cell biology 68 23533418
1997 Bcl-x expression influences keratinocyte cell survival but not terminal differentiation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 68 9185996
2016 Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis. Nature microbiology 67 27572165
2010 The anti-apoptotic protein BCL2L1/Bcl-xL is neutralized by pro-apoptotic PMAIP1/Noxa in neuroblastoma, thereby determining bortezomib sensitivity independent of prosurvival MCL1 expression. The Journal of biological chemistry 63 20051518
2008 Nucleolin stabilizes Bcl-X L messenger RNA in response to UVA irradiation. Cancer research 63 18281479
1997 Bcl-x protects primary B cells against Fas-mediated apoptosis. Journal of immunology (Baltimore, Md. : 1950) 62 9366408
2006 BCL-xL regulates synaptic plasticity. Molecular interventions 59 16960143
2000 Bcl-xS and Bax induce different apoptotic pathways in PC12 cells. Oncogene 59 10777212
2019 The Structural Biology of Bcl-xL. International journal of molecular sciences 58 31067648
2020 BCL-xL/BCL2L1 is a critical anti-apoptotic protein that promotes the survival of differentiating pancreatic cells from human pluripotent stem cells. Cell death & disease 57 32424151
2007 Protein kinase C-dependent control of Bcl-x alternative splicing. Molecular and cellular biology 56 17923691
2018 Specific G-quadruplex ligands modulate the alternative splicing of Bcl-X. Nucleic acids research 55 29156002
2001 Transcriptional regulation of the BCL-X gene by NF-kappaB is an element of hypoxic responses in the rat brain. Neurochemical research 54 11519724
2015 Conformation of BCL-XL upon Membrane Integration. Journal of molecular biology 52 25731750
2010 Fragment-based deconstruction of Bcl-xL inhibitors. Journal of medicinal chemistry 52 20192224
2014 Long non-coding RNA INXS is a critical mediator of BCL-XS induced apoptosis. Nucleic acids research 49 24992962
2015 Ceramide channels: destabilization by Bcl-xL and role in apoptosis. Biochimica et biophysica acta 48 26215742
2007 Modulation of bcl-xL in tumor cells regulates angiogenesis through CXCL8 expression. Molecular cancer research : MCR 47 17699103
2015 Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer. Proceedings of the National Academy of Sciences of the United States of America 46 26401016
2021 BCLXL gene therapy moderates neuropathology in the DBA/2J mouse model of inherited glaucoma. Cell death & disease 45 34376637
2019 Exogenous Let-7a-5p Induces A549 Lung Cancer Cell Death Through BCL2L1-Mediated PI3Kγ Signaling Pathway. Frontiers in oncology 44 31508368
2017 BCL-XL directly modulates RAS signalling to favour cancer cell stemness. Nature communications 44 29066722
2008 Significance of Bcl-xL in human colon carcinoma. World journal of gastroenterology 44 18494061
1997 Bcl-2, Bax and Bcl-x expression following hypoxia-ischemia in the infant rat brain. Acta neuropathologica 44 9444360
2003 Regulation of Bcl-xL expression by H2O2 in cardiac myocytes. The Journal of biological chemistry 43 12721309
2006 Haloperidol induces apoptosis via the sigma2 receptor system and Bcl-XS. The pharmacogenomics journal 42 16462815
2004 bcl-xL is critical for dendritic cell survival in vivo. Journal of immunology (Baltimore, Md. : 1950) 42 15383573
2021 Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation. Journal of experimental & clinical cancer research : CR 41 34118966
2016 Physiological restraint of Bak by Bcl-xL is essential for cell survival. Genes & development 41 27198225
2005 Enhancing TRAIL-induced apoptosis by Bcl-X(L) siRNA. Cancer biology & therapy 41 15846108
1998 Bcl-x is a regulatory factor of apoptosis and differentiation in megakaryocytic lineage cells. Experimental hematology 41 9502620
2015 Bcl-xL is necessary for neurite outgrowth in hippocampal neurons. Antioxidants & redox signaling 38 24787232
2015 Propofol-induced rno-miR-665 targets BCL2L1 and influences apoptosis in rodent developing hippocampal astrocytes. Neurotoxicology 37 26254736
2015 Pharmacological inhibition of Bcl-xL sensitizes osteosarcoma to doxorubicin. Oncotarget 36 26416351
2007 Bcl2/bcl-xL inhibitor engenders apoptosis and increases chemosensitivity in mesothelioma. Cancer biology & therapy 36 17224645
2005 Spontaneous immunity against Bcl-xL in cancer patients. Journal of immunology (Baltimore, Md. : 1950) 35 16081848
2022 SF3B1 inhibition disrupts malignancy and prolongs survival in glioblastoma patients through BCL2L1 splicing and mTOR/ß-catenin pathways imbalances. Journal of experimental & clinical cancer research : CR 34 35086552
2014 Bcl-xL in neuroprotection and plasticity. Frontiers in physiology 31 25278904
2012 BCL2L1 (BCL-X) promotes survival of adult and developing retinal ganglion cells. Molecular and cellular neurosciences 31 22836101
2022 Roles and Regulation of BCL-xL in Hematological Malignancies. International journal of molecular sciences 29 35216310
2021 Bcl-xL: A Focus on Melanoma Pathobiology. International journal of molecular sciences 29 33803452
2019 Inhibiting the expression of anti-apoptotic genes BCL2L1 and MCL1, and apoptosis induction in glioblastoma cells by microRNA-342. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 31751869
2010 Inhibition of Bcl-2 and Bcl-X enhances chemotherapy sensitivity in hepatoblastoma cells. Pediatric blood & cancer 29 20680965
2003 Bcl-x(L) and Akt cooperate to promote leukemogenesis in vivo. Oncogene 29 12569361
1998 Butyrate attenuates BCLX(L) expression in human fibroblasts and acts in synergy with ionizing radiation to induce apoptosis. Radiation research 29 9457899
2017 PRMT2 interacts with splicing factors and regulates the alternative splicing of BCL-X. Journal of biochemistry 28 28057797
1998 BCL-X and the apoptotic machinery of lymphoma cells. Leukemia & lymphoma 28 9613974
2020 Dihydroartemisinin inhibits the tumorigenesis and invasion of gastric cancer by regulating STAT1/KDR/MMP9 and P53/BCL2L1/CASP3/7 pathways. Pathology, research and practice 27 33370709
2019 Nonconserved miR-608 suppresses prostate cancer progression through RAC2/PAK4/LIMK1 and BCL2L1/caspase-3 pathways by targeting the 3'-UTRs of RAC2/BCL2L1 and the coding region of PAK4. Cancer medicine 26 31389670
2002 Bcl-X(L) and calyculin A prevent translocation of Bax to mitochondria during apoptosis. Biochemical and biophysical research communications 26 11883953
2023 Alternative splicing of BCL-x is controlled by RBM25 binding to a G-quadruplex in BCL-x pre-mRNA. Nucleic acids research 25 37811881
2003 Bcl-x(L) antisense oligonucleotides radiosensitise colon cancer cells. British journal of cancer 25 14520471
2022 Targeting BCL-XL in fibrolamellar hepatocellular carcinoma. JCI insight 24 36073545
2006 Bcl-x(L) expression in vivo in rheumatoid synovium. Clinical rheumatology 24 16572289
2004 FAST is a BCL-X(L)-associated mitochondrial protein. Biochemical and biophysical research communications 24 15110758
2003 Expression of Bcl-x(S) in Xenopus oocytes induces BH3-dependent and caspase-dependent cytochrome c release and apoptosis. Molecular cancer research : MCR 24 12556558
2021 Oxidative stress battles neuronal Bcl-xL in a fight to the death. Neural regeneration research 23 32788441
2019 BMPRII deficiency impairs apoptosis via the BMPRII-ALK1-BclX-mediated pathway in pulmonary arterial hypertension. Human molecular genetics 23 30809644
2016 rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes. Journal of neurochemistry 23 27121046
1997 Bcl-x and the regulation of survival in the immune system. Immunologic research 23 9212361
2016 Modulation of Bcl-x Alternative Splicing Induces Apoptosis of Human Hepatic Stellate Cells. BioMed research international 21 27579319
2002 Bcl-x is not required for maintenance of follicles and corpus luteum in the postnatal mouse ovary. Biology of reproduction 21 11804960
2008 Protein phosphatase 1 activation and alternative splicing of Bcl-X and Mcl-1 by EGCG + ibuprofen. Journal of cellular biochemistry 20 18348186
2001 Expression of bcl(xs) and c-myc in atretic follicles of mouse ovary. Reproductive biomedicine online 20 12513859
2021 NOXA-mediated degradation of MCL1 and BCL2L1 causes apoptosis of daunorubicin-treated human acute myeloid leukemia cells. Journal of cellular physiology 19 33982799
2012 Zebrafish bcl2l is a survival factor in thyroid development. Developmental biology 19 22537491
2006 p21Cip1 protection against hyperoxia requires Bcl-XL and is uncoupled from its ability to suppress growth. The American journal of pathology 19 16723699

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