Affinage

BCLAF1

Bcl-2-associated transcription factor 1 · UniProt Q9NYF8

Length
920 aa
Mass
106.1 kDa
Annotated
2026-06-09
64 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCLAF1 is a multifunctional nuclear protein that integrates transcriptional regulation, RNA processing, and stress signaling to control cell fate decisions across development, immunity, and tumorigenesis (PMID:10330179, PMID:19008920, PMID:40435510). It was originally identified as a DNA-binding transcriptional repressor sequestered in the cytoplasm by anti-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL, E1B 19K), with sustained overexpression driving apoptosis (PMID:10330179). As a chromatin-associated factor it occupies target promoters in partnership with diverse transcription factors and cofactors: it co-occupies the TP53 promoter with PKCδ to drive p53-dependent apoptosis (PMID:17938203), cooperates with C/EBPβ and NF-κB subunits (p65/c-Rel during senescence, p50 to induce the caspase-8 antagonist c-FLIP) (PMID:26794446, PMID:34693625), partners with SPIC to enforce pre-B cell development (PMID:31644907), forms a repressive complex with TET2 to control DNA methylation at target loci (PMID:35660018), and positively autoregulates its own transcription via a complex with p85β, TRIM28, and ZNF263 (PMID:40016211). In parallel, BCLAF1 functions as an SR-like splicing and mRNA-export factor that associates with the exon junction complex and core spliceosome and, together with THRAP3, controls splicing and nuclear export of DNA-damage-response transcripts including ATM mRNA, thereby safeguarding genome stability (PMID:23778535, PMID:29112714, PMID:41648520). It additionally participates directly in DNA repair by associating with γH2AX, stabilizing the Ku70/DNA-PKcs NHEJ complex, and acting as a BACH1- and BRCA1-dependent partner in homologous recombination (PMID:22833098, PMID:35930920). BCLAF1 is a transcriptional target and stabilizer of HIF-1α under hypoxia, forming a positive feedback loop that drives angiogenesis and, via CUL3-dependent PHD2 degradation, sustains HIF-1α and PD-L1 even under normoxia (PMID:30367150, PMID:32029898, PMID:37906282). Its activity is tuned post-translationally by PKCδ, BCKDK-mediated phosphorylation at Ser285 (promoting MYC transcription and glycolysis), and phospho-dependent recruitment of PP1 via SDS22, and its nuclear translocation is gated by LAMTOR2 and lncCIRBIL (PMID:17938203, PMID:40442441, PMID:30661852, PMID:39990659, PMID:33483496). BCLAF1 acts as a restriction factor against cytomegalovirus and alphaherpesviruses and supports type I interferon signaling by maintaining STAT phosphorylation and ISGF3 promoter binding; viral proteins (HCMV pp71/UL35, HSV-1/PRV US3) neutralize it by proteasomal degradation (PMID:22645331, PMID:30682178). In vivo, BCLAF1 is required for lung smooth muscle organization, peripheral T-cell homeostasis, and hematopoietic stem cell self-renewal, with knockout cells showing no intrinsic apoptosis defect, refining its originally postulated proapoptotic role (PMID:19008920, PMID:40435510).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Established BCLAF1's founding identity as a DNA-binding transcriptional repressor whose activity is held in check by anti-apoptotic Bcl-2 proteins, linking it to apoptotic control.

    Evidence Yeast two-hybrid screen, in vitro DNA binding, reporter assay, and overexpression apoptosis assay in HeLa cells

    PMID:10330179

    Open questions at the time
    • Direct DNA target sequences and endogenous repressed genes not defined
    • Whether apoptosis is a physiological function untested in vivo at this stage
  2. 2004 High

    Mapped a high-affinity emerin interaction and showed apoptosis-regulated relocalization, tying BCLAF1 to the nuclear envelope and a disease-relevant mutation.

    Evidence Equilibrium binding assay, alanine-scanning mutagenesis, and immunofluorescence in HeLa cells

    PMID:15009215

    Open questions at the time
    • Functional consequence of emerin binding for BCLAF1 activity not established
    • Significance of nuclear-interior dot localization unresolved
  3. 2007 High

    Defined a concrete transcriptional target and upstream kinase by showing PKCδ interacts with BCLAF1 to co-occupy and activate the TP53 promoter, enabling genotoxic stress apoptosis.

    Evidence Co-IP, ChIP co-occupancy at CPE-TP53, reporter assay, and RNAi with apoptosis readout

    PMID:17938203

    Open questions at the time
    • Whether PKCδ directly phosphorylates BCLAF1 not shown
    • Broader PKCδ-dependent target gene set undefined
  4. 2008 High

    Revealed BCLAF1's essential developmental and immune roles in vivo and overturned the assumption that it is intrinsically proapoptotic.

    Evidence Targeted knockout mice with lung developmental and T-cell compartment analysis

    PMID:19008920

    Open questions at the time
    • Molecular mechanism behind lung and T-cell phenotypes not defined
    • Reconciliation with cell-line proapoptotic data left open
  5. 2011 High

    Placed BCLAF1 under NF-κB/Sirt1-controlled epigenetic regulation, showing its expression is dynamically gated during T-cell activation.

    Evidence ChIP, Co-IP, histone H3K56 acetylation analysis, and siRNA in T cells

    PMID:21454709

    Open questions at the time
    • Direct BCLAF1 effector genes in activated T cells not identified
    • Whether BCLAF1 feeds back on NF-κB unaddressed at this stage
  6. 2012 High

    Connected BCLAF1 to the DNA damage response and to viral restriction, establishing dual roles in NHEJ-based repair and innate antiviral defense.

    Evidence Co-IP, γH2AX co-localization and NHEJ assays; viral degradation and replication assays for HCMV

    PMID:22645331 PMID:22833098

    Open questions at the time
    • Mechanism by which BCLAF1 stabilizes Ku70/DNA-PKcs not structurally defined
    • How tumor cells suppress BCLAF1 unresolved
  7. 2013 Medium

    Defined BCLAF1 as an RNA-processing factor at active transcription loci that restricts mRNA nuclear export, distinguishing it functionally from its paralog TRAP150.

    Evidence Reporter-locus microscopy, EJC (Magoh) overlap, siRNA, and nuclear/cytoplasmic fractionation with RT-PCR

    PMID:23778535

    Open questions at the time
    • Direct RNA substrates not catalogued
    • Molecular basis of export restriction unknown
  8. 2014 High

    Showed BCLAF1 is itself a splicing-regulated gene whose SRSF10-driven exon5a isoform has oncogenic activity, linking its isoform identity to tumor phenotypes.

    Evidence Splicing assay, siRNA, overexpression, and tumorigenicity assays in colorectal cancer cells

    PMID:25091051

    Open questions at the time
    • Functional difference between isoforms at the protein level not defined
    • Whether isoform switching alters partner binding unknown
  9. 2016 High

    Defined BCLAF1 as an NF-κB-induced transducer to C/EBPβ during therapy-induced senescence, controlling SASP cytokine output and tumor suppression.

    Evidence ChIP, Co-IP with C/EBPβ leucine zipper, reporter assay, siRNA, and xenograft model

    PMID:26794446

    Open questions at the time
    • Whether BCLAF1 acts as transcription factor or cofactor at IL-6/IL-8 loci not fully resolved
    • Generality across senescence triggers untested
  10. 2017 High

    Established a unifying mechanism whereby BCLAF1/THRAP3 control DDR via selective splicing and export of repair transcripts, and linked BCLAF1 to mitotic transcript control.

    Evidence siRNA, DNA damage sensitivity and repair assays, splicing/export analysis, and mitotic phenotype/RT-PCR readouts

    PMID:28895891 PMID:29112714

    Open questions at the time
    • RNA-binding specificity determinants not defined
    • Direct versus indirect effects on mitotic regulators unresolved
  11. 2018 High

    Identified a HIF-1α/BCLAF1 positive feedback loop and a Cry2-coupled mRNA-stabilizing function, expanding BCLAF1's roles into hypoxic angiogenesis and circadian myogenesis.

    Evidence shRNA, reporter and bZIP domain-deletion assays, xenograft for HIF1A; Co-IP, mRNA stability assays and Cry2 KO mice for circadian function

    PMID:29466738 PMID:30367150

    Open questions at the time
    • How BCLAF1 stabilizes HIF-1α mechanistically not yet defined at this stage
    • Determinants of Cry2-selective mRNA targeting unknown
  12. 2019 High

    Defined BCLAF1 as a STAT/ISGF3-supporting interferon effector, a SPIC-recruited B-cell developmental regulator, and a phospho-dependent PP1 substrate, broadening its signaling and post-translational regulatory repertoire.

    Evidence Co-IP, ChIP/DNA binding, CRISPR KO and antiviral assays (IFN); Co-IP and ChIP-seq (SPIC); X-ray crystallography of SDS22 with phospho-BCLAF1 binding

    PMID:30661852 PMID:30682178 PMID:31644907

    Open questions at the time
    • Phosphosites recognized by SDS22/PP1 not mapped at this stage
    • How US3 selects BCLAF1 for degradation unknown
  13. 2020 High

    Resolved the HIF-1α stabilization mechanism by showing nuclear BCLAF1 binds HIF-1α directly and is required to sustain it during prolonged hypoxia.

    Evidence ChIP, Co-IP, CRISPR knockout, HIF-1α stability assays, and xenograft model

    PMID:32029898

    Open questions at the time
    • Biochemical basis of HIF-1α protection by BCLAF1 not fully defined
    • Whether stabilization requires BCLAF1 chromatin function unresolved
  14. 2021 High

    Established BCLAF1 as an NF-κB-p50-dependent anti-apoptotic transcriptional driver of c-FLIP and as a lncRNA-gated mediator of cardiac injury, refining its context-dependent cell-death roles.

    Evidence Co-IP with p50, reporter assay, apoptosis/necroptosis assays and intestinal injury model (CFLAR); RNA-protein binding, nuclear translocation, and transgenic I/R models (lncCIRBIL)

    PMID:33483496 PMID:34693625

    Open questions at the time
    • How the same protein switches between pro- and anti-apoptotic outputs not unified
    • lncCIRBIL binding site on BCLAF1 not mapped
  15. 2021 Medium

    Linked ATM-activated BCLAF1 to PD-L1 stability, implicating BCLAF1 in immune evasion downstream of DNA damage.

    Evidence Mass spectrometry, Co-IP, ubiquitination assay, siRNA, and T-cell co-culture

    PMID:34251713

    Open questions at the time
    • Direct mechanism by which BCLAF1 protects PD-L1 from ubiquitination unclear
    • Single-lab MS-based interaction
  16. 2022 High

    Expanded BCLAF1's interactome and PD-L1 regulation, revealing TET2 repressive complex formation, BACH1/BRCA1-dependent HR, competitive SPOP inhibition stabilizing PD-L1, and a BCL2-linked smooth-muscle role.

    Evidence LC-MS/MS, Co-IP, PLA and ChIP (TET2); affinity purification and HR assays (BACH1); SBC-motif mutagenesis and ubiquitination assays (SPOP); siRNA, PLA and lineage tracing (BCL2/SMC)

    PMID:35321563 PMID:35660018 PMID:35930920 PMID:38340178

    Open questions at the time
    • How BCLAF1 partitions among these complexes within a cell unknown
    • Stoichiometry and mutual exclusivity of partners undefined
  17. 2023 Medium

    Structurally placed BCLAF1 in a defined TEB complex with THRAP3 and ERH and resolved an alternate normoxic HIF-1α stabilization route via CUL3-dependent PHD2 degradation.

    Evidence Cross-linking mass spectrometry of endogenous complexes (TEB); Co-IP, immunofluorescence and PHD2 ubiquitination assays (CUL3)

    PMID:35865489 PMID:37906282

    Open questions at the time
    • Functional role of the TEB complex not tested
    • Whether CUL3-PHD2 and direct HIF-1α binding mechanisms coexist or compete unresolved
  18. 2024 High

    Connected BCLAF1 to m6A-RNA metabolism via YTHDF2 antagonism and to lysosomal/mTOR-adjacent signaling via LAMTOR2-gated nuclear translocation, expanding its post-transcriptional and localization control.

    Evidence MS, Co-IP, GST pull-down, MeRIP/RIP-seq (YTHDF2); IP-MS, nuclear translocation, knockdown and OA model (LAMTOR2)

    PMID:38636894 PMID:39990659

    Open questions at the time
    • Whether BCLAF1 alters YTHDF2 catalytic engagement or sequesters it not distinguished
    • How LAMTOR2 controls BCLAF1 import mechanistically unknown
  19. 2025 Medium

    Defined upstream phospho-control by BCKDK at Ser285 and a cofactor partnership with MED23, linking BCLAF1 to MYC-driven glycolysis, drug resistance, and autophagy/senescence transcriptional programs.

    Evidence Co-IP, S285 phosphorylation assay, ChIP and glycolysis assays (BCKDK/MYC); Co-IP, PLA, RNA-seq and ChIP (MED23/NUPR1)

    PMID:39366174 PMID:40442441

    Open questions at the time
    • How Ser285 phosphorylation alters BCLAF1 DNA binding biochemically unresolved
    • Single-lab studies awaiting independent confirmation
  20. 2025 High

    Established BCLAF1's autoregulatory transcription circuit, its requirement for HSC self-renewal, and a dual transcription/splicing mechanism controlling POLR2A and chromatin accessibility.

    Evidence Co-IP and ChIP-seq with p85β/TRIM28/ZNF263 (autoregulation); conditional KO, scRNA-seq and transplantation (HSC); ATAC-seq, CUT&Tag and RIP with SNRPA (POLR2A)

    PMID:40016211 PMID:40220379 PMID:40435510

    Open questions at the time
    • How autoregulation is set or reset across cell states unknown
    • Whether the POLR2A dual mechanism generalizes beyond esophageal carcinoma untested
  21. 2025 Medium

    Proposed condensate-based and splicing-based protective mechanisms, with BCLAF1 phase separation shielding PTK2 from degradation and BCLAF1-dependent ATF4 splicing sustaining amino-acid metabolism.

    Evidence LLPS imaging, ubiquitination and K926 mutagenesis assays (PTK2, preprint); Co-IP with spliceosome, splicing analysis, metabolomics and venetoclax sensitivity (ATF4, preprint)

    PMID:41648520 PMID:bio_10.1101_2025.02.04.636487

    Open questions at the time
    • Both findings are preprints awaiting peer review
    • Determinants of BCLAF1 condensate formation and client selection not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single protein coordinates its DNA-binding/transcription, splicing/export, DNA-repair, and condensate functions, and what determines its partitioning among the many mutually exclusive partner complexes and post-translational states.
  • No structural model of full-length BCLAF1 or its domain-specific partner engagement
  • Rules governing context-dependent pro- versus anti-apoptotic outputs unknown
  • Whether splicing, transcription, and condensate roles are temporally or spatially separated undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003723 RNA binding 5 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 3 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0000228 nuclear chromosome 5 GO:0005634 nucleus 5 GO:0005654 nucleoplasm 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-8953854 Metabolism of RNA 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
BACH1C/EBPΒCUL3HIF1ASPOPTET2THRAP3YTHDF2
Complex memberships
Ku70/DNA-PKcs NHEJ complexSPIC/BCLAF1 transcription complexTEB complex (BCLAF1-THRAP3-ERH)TET2-BCLAF1 repression complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 BCLAF1 (Btf) was identified as a novel protein that interacts with anti-apoptotic proteins E1B 19K, Bcl-2, and Bcl-xL but not with pro-apoptotic Bax. Btf binds DNA in vitro and represses transcription in reporter assays. E1B 19K, Bcl-2, and Bcl-xL sequester Btf in the cytoplasm and block its transcriptional repression activity. Sustained overexpression of Btf in HeLa cells induced apoptosis, which was inhibited by E1B 19K. Yeast two-hybrid screen, DNA binding assay in vitro, transcriptional reporter assay, subcellular localization, overexpression/apoptosis assay Molecular and cellular biology High 10330179
2004 Emerin binds BCLAF1 (Btf) with an equilibrium affinity (KD) of ~100 nM; this interaction was mapped to two regions of emerin flanking its lamin-binding domain. Disease-causing emerin mutation S54F selectively disrupts emerin binding to Btf without affecting binding to BAF, lamin A, or GCL. In non-apoptotic HeLa cells, endogenous Btf localizes to dot-like structures in the nuclear interior; upon Fas-induced apoptosis, Btf redistributes to a zone near the nuclear envelope, indicating apoptosis-regulated subcellular localization. Yeast two-hybrid, biochemical binding assay (equilibrium affinity), clustered alanine-substitution mutagenesis, indirect immunofluorescence European journal of biochemistry High 15009215
2007 PKCδ transactivates TP53 expression by interacting with BCLAF1 (Btf) and co-occupying the TP53 core promoter element (CPE-TP53). Inhibition of PKCδ activity decreases Btf affinity for CPE-TP53, reducing TP53 mRNA and protein levels. RNAi-mediated disruption of Btf-mediated TP53 transcription suppresses TP53-dependent apoptosis following genotoxic stress. Reporter assay (promoter activity), co-immunoprecipitation, ChIP (co-occupancy of CPE-TP53), RNAi knockdown with apoptosis readout Molecular and cellular biology High 17938203
2008 Bclaf1 knockout mice demonstrate that Bclaf1 is required for proper spatial and temporal organization of smooth muscle lineage during the saccular stage of lung development and is essential for peripheral T-cell homeostasis. Bclaf1-deficient cells showed no defect in apoptosis in response to various apoptotic stimuli, contradicting its postulated role as a proapoptotic protein in vivo. Targeted gene knockout in mice, histological and cellular analysis of lung development and T-cell compartment Cell death and differentiation High 19008920
2011 Sirt1 suppresses Bclaf1 transcription by deacetylating histone H3K56 at the bclaf1 promoter, counteracting p300-mediated H3K56 acetylation. Sirt1 is recruited to the bclaf1 promoter upon TCR/CD28 stimulation through a complex with p300 and NF-κB subunit Rel-A; blocking Rel-A nuclear translocation inhibits Sirt1 binding. Knockdown of Bclaf1 suppresses hyperactivation of Sirt1-null T cells. ChIP assay, siRNA knockdown, co-immunoprecipitation, histone acetylation analysis, T cell activation assays The Journal of biological chemistry High 21454709
2012 BCLAF1 shows enhanced association with γH2AX specifically under high-dose ionizing radiation. BCLAF1 promotes apoptosis of irreparably damaged cells by disrupting p21-mediated inhibition of Caspase/cyclin E-dependent mitochondrial pathways. BCLAF1 co-localizes with γH2AX foci and stabilizes the Ku70/DNA-PKcs complex, facilitating NHEJ-based DSB repair in surviving cells. In tumor cells, BCLAF1 is intrinsically suppressed, leading to formation of anti-apoptotic Ku70-Bax complexes and disrupted Ku70/DNA-PKcs complexes. Co-immunoprecipitation, immunofluorescence co-localization, NHEJ repair assay, apoptosis assays Cell death & disease Medium 22833098
2012 BCLAF1 functions as a restriction factor against human cytomegalovirus (HCMV). Immediately after infection, viral pp71 and UL35 proteins (delivered via virions) direct proteasomal degradation of BCLAF1. At late infection stages, virus-encoded miR-UL112-1 down-regulates BCLAF1. In the absence of BCLAF1 neutralization, viral gene expression and replication are inhibited. Protein degradation assay, viral miRNA functional assay, viral gene expression/replication assay with BCLAF1 knockdown/rescue Proceedings of the National Academy of Sciences of the United States of America High 22645331
2013 BCLAF1 (Btf) localizes at active transcription loci in a RNA Pol II-dependent manner and shows overlap with the exon junction complex protein Magoh. Btf depletion causes increased β-tropomyosin reporter transcripts and global increase of endogenous polyadenylated RNA in the cytoplasm, indicating a role for Btf in restricting mRNA nuclear export; TRAP150 depletion did not produce this effect. Fluorescence microscopy (localization at reporter gene loci), siRNA knockdown, nuclear/cytoplasmic fractionation with RT-PCR Nucleus (Austin, Tex.) Medium 23778535
2014 The splicing factor SRSF10 stimulates inclusion of BCLAF1 alternative exon5a, producing a specific BCLAF1 protein isoform. Knockdown of this exon5a-containing isoform inhibited growth of colorectal cancer cells, while its overexpression increased tumorigenic potential. Splicing assay, siRNA knockdown, overexpression, cell growth and tumorigenicity assays Nature communications High 25091051
2016 BCLAF1 is upregulated through the ATM/Nemo/NF-κB pathway during doxorubicin-induced senescence (TIS) and is a direct transcriptional target of p65 and c-Rel. BCLAF1 induction by NF-κB is required for C/EBPβ upregulation and IL-6/IL-8 transcription during TIS. BCLAF1 interacts with the leucine zipper region of C/EBPβ to cooperate in upregulating IL-8. BCLAF1 is required for effectiveness of doxorubicin-induced tumor suppression in a xenograft model. ChIP, co-immunoprecipitation, siRNA knockdown, reporter assay, xenograft tumor model Cell death and differentiation High 26794446
2017 BCLAF1 and THRAP3 promote the DNA damage response by selective mRNA splicing and nuclear export of DDR transcripts, including ATM kinase mRNA. Loss of THRAP3 and/or BCLAF1 leads to sensitivity to DNA damaging agents, defective DNA repair, and genomic instability. Cancer-associated mutations in THRAP3 result in deregulated processing of THRAP3/BCLAF1-regulated transcripts and defective DNA repair. siRNA knockdown, DNA damage sensitivity assays, DNA repair assays, genomic instability assays, mRNA splicing/export analysis Nucleic acids research High 29112714
2017 Depletion of BCLAF1 (Btf) and/or TRAP150 causes mitotic chromosome misalignment defects and altered abundance of transcripts encoding mitotic regulators, suggesting that Btf controls transcript abundance of mitotic checkpoint regulators, thereby affecting mitotic progression. siRNA knockdown, immunofluorescence (mitotic defects), RT-PCR (transcript levels) International journal of molecular sciences Medium 28895891
2018 BCLAF1 promotes HIF1A transcription via its bZIP domain in hepatocellular carcinoma cells, leading to increased transcription of VEGFA, TGFB, and EPO, which promote HCC-associated angiogenesis. HIF-1α levels and microvessel density decrease after shRNA-mediated BCLAF1 knockdown in xenograft tumors. A positive feedback loop exists: HIF-1α induces BCLAF1, which in turn stabilizes HIF-1α expression. shRNA knockdown, reporter assay, domain deletion (bZIP), xenograft tumor model, qRT-PCR, Western blot Oncogene Medium 30367150
2018 Cry2 (but not Cry1) specifically interacts with BCLAF1 to stabilize mRNAs encoding cyclin D1 and Tmem176b, regulating circadian patterns of myoblast proliferation and myotube formation. BCLAF1 knockdown recapitulates Cry2 knockdown phenotypes: premature cell cycle exit and inefficient myogenic cell fusion. Co-immunoprecipitation, mRNA stability assay, siRNA knockdown, Cry2 knockout mice, myogenic differentiation assays Cell reports High 29466738
2019 BCLAF1 is degraded during alphaherpesvirus PRV and HSV-1 infection through the viral protein US3. BCLAF1 functions in type I interferon signaling by maintaining efficient STAT1 and STAT2 phosphorylation in response to IFNα and by directly interacting with ISRE sequences and STAT2 to facilitate ISGF3 binding for gene transcription. Knockdown or knockout of BCLAF1 significantly impairs IFNα-mediated gene transcription and antiviral activity. Protein degradation assay, Co-immunoprecipitation, ChIP/DNA binding assay, siRNA/CRISPR knockout, antiviral functional assays, STAT phosphorylation assay PLoS pathogens High 30682178
2019 Crystal structure of SDS22 reveals a large basic surface patch that enables binding of a phosphorylated form of splicing factor BCLAF1. Biochemical studies show SDS22 acts as a 'third' subunit of multiple PP1 holoenzymes and recruits phospho-BCLAF1. X-ray crystallography (SDS22 structure), biochemical binding assays, modeling Structure (London, England : 1993) High 30661852
2019 RAG DNA double-strand breaks in pre-B cells activate a SPIC/BCLAF1 transcription factor complex. SPIC recruits BCLAF1 to gene-regulatory elements controlling expression of key B cell developmental genes. The SPIC/BCLAF1 complex suppresses SYK tyrosine kinase expression and enforces the transition from large to small pre-B cells. Co-immunoprecipitation, ChIP-seq, gene expression analysis, B cell developmental assays in pre-B cell models Cell reports High 31644907
2020 BCLAF1 is a direct transcriptional target of HIF-1 and is upregulated during hypoxia. BCLAF1 binds HIF-1α in the nucleus, and this interaction is required for BCLAF1 to stabilize HIF-1α during long-term hypoxia. BCLAF1 knockout cells show greatly reduced HIF-1α protein stability and impaired induction of HIF-1 target gene transcription after prolonged hypoxia. ChIP (HIF-1 binding to BCLAF1 promoter), Co-immunoprecipitation (BCLAF1-HIF-1α), CRISPR knockout, HIF-1α stability assays, xenograft tumor model Oncogene High 32029898
2021 BCLAF1 exerts anti-apoptotic function in TNF signaling by promoting transcription of CFLAR (encoding c-FLIP, a caspase 8 antagonist) downstream of NF-κB activation. BCLAF1 binds to the p50 subunit of NF-κB, which is required for BCLAF1 to stimulate CFLAR transcription. BCLAF1 depletion sensitizes cells to TNF-induced apoptosis but not necroptosis, and exacerbates TNF-induced small intestine injury in mice. Co-immunoprecipitation (BCLAF1-p50 interaction), siRNA knockdown, reporter assay, apoptosis/necroptosis assays, in vivo mouse model (siRNA administration) EMBO reports High 34693625
2021 lncCIRBIL directly binds to BCLAF1 protein and inhibits its nuclear translocation. Cardiomyocyte-specific Bclaf1 overexpression worsens cardiac I/R injury, while partial Bclaf1 knockout mitigates it. Partial Bclaf1 knockout abrogates the detrimental effects of lncCIRBIL knockout, placing Bclaf1 downstream of lncCIRBIL in cardiac I/R injury. RNA-protein binding assay (lncCIRBIL-BCLAF1 interaction), nuclear translocation assay, transgenic overexpression and knockout mice, I/R injury model Nature communications Medium 33483496
2021 ATM activation in response to ionizing radiation leads to BCLAF1-dependent regulation of PD-L1 stability. BCLAF1 depletion decreases PD-L1 expression by promoting its ubiquitination. CMTM6 is upregulated in response to IR and participates in BCLAF1-dependent PD-L1 upregulation. The ATM/BCLAF1/PD-L1 axis was identified by mass spectrometry and validated by co-immunoprecipitation. Mass spectrometry (PD-L1 interactome), co-immunoprecipitation, ubiquitination assay, siRNA knockdown, T cell co-culture assay Cancer science Medium 34251713
2022 TET2 and BCLAF1 form a transcription repression complex in CRC cells. The TET2-BCLAF1 complex binds multiple elements around CCGG sites at the Ascl2 promoter and restrains its hypermethylation by inducing hydroxymethylation. BCLAF1 was identified as a TET2 interactor by LC-MS/MS and validated by co-immunoprecipitation, immunofluorescence co-localization, and proximity ligation assays. LC-MS/MS, co-immunoprecipitation, immunofluorescence co-localization, proximity ligation assay, ChIP-qPCR, glucosylated hydroxymethyl-qPCR The Journal of biological chemistry High 35660018
2022 BCLAF1 physically interacts with SPOP (an E3 ubiquitin ligase) via an SPOP-binding consensus (SBC) motif on BCLAF1, competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Mutation of the BCLAF1-SBC motif disrupts regulation of the SPOP-PD-L1 axis. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis of SBC motif, T cell co-culture model, in vitro competition assay Cellular and molecular life sciences : CMLS High 38340178
2022 BCLAF1 silencing in smooth muscle cells (SMCs) led to downregulation of BCL2 and SMC markers, reduced proliferation, and increased apoptosis. oxLDL-induced transdifferentiation of SMCs was accompanied by BCLAF1 upregulation, and BCLAF1 silencing during oxLDL exposure preserved MYH11 expression and prevented SMC transdifferentiation. BCLAF1 was shown to interact with BCL2 by proximity ligation assay in plaque cells. siRNA knockdown, proximity ligation assay (BCLAF1-BCL2 interaction), oxLDL treatment, immunohistochemistry, lineage-tracing mouse model Arteriosclerosis, thrombosis, and vascular biology Medium 35321563
2022 BCLAF1 was identified as a binding partner of BACH1 by tandem protein affinity purification. BCLAF1 constitutively interacts with BACH1 regardless of DNA damage, but in response to DNA damage, BCLAF1 is recruited to DNA damage sites in a BACH1- and BRCA1-dependent manner. BCLAF1-deficient cells are defective for DSB-initiated homologous recombination, but RAD51 foci formation is intact. Tandem protein affinity purification, co-immunoprecipitation, recruitment to DNA damage sites (foci assay), HR repair assay, RAD51 foci assay DNA repair Medium 35930920
2023 Cross-linking mass spectrometry (XL-MS) of endogenous protein complexes identified crosslinks between BCLAF1, THRAP3, and ERH, mapping interaction surfaces to non-disordered portions of both BCLAF1 and THRAP3, suggesting these three proteins form a novel complex (TEB complex). Cross-linking mass spectrometry (XL-MS with DSSO crosslinker) after immunoprecipitation of endogenous complexes Wellcome open research Medium 35865489
2023 BCLAF1 promotes HIF-1α accumulation under normoxia by interacting with CUL3 (Cullin 3) ubiquitin ligase, promoting ubiquitination and degradation of PHD2 (prolyl hydroxylase domain protein 2), thereby stabilizing HIF-1α. This leads to HIF-1α-dependent PD-L1 transcription. BCLAF1-CUL3 interaction validated by co-immunoprecipitation and immunofluorescence. Co-immunoprecipitation, immunofluorescence, PHD2 ubiquitination assay, Western blot, RT-qPCR Cancer immunology, immunotherapy : CII Medium 37906282
2024 BCLAF1 interacts with YTHDF2 (an m6A reader) in ESCC cells, reducing YTHDF2's tumor-suppressive activities. BCLAF1-YTHDF2 interaction was validated by mass spectrometry, co-localization, co-immunoprecipitation, and GST pull-down. This interaction leads to stabilization of SIX1 mRNA (normally degraded by YTHDF2), promoting glycolysis and cancer progression in an m6A-specific manner. Mass spectrometry, co-immunoprecipitation, GST pull-down, MeRIP-seq, RIP-seq, transcriptomic analysis Cancer letters High 38636894
2024 BCLAF1 interacts with LAMTOR2, and LAMTOR2 regulates the nuclear translocation of BCLAF1 in chondrocytes. BCLAF1 knockdown inhibits catabolic factor expression and apoptosis in chondrocytes while promoting anabolic factors, and intra-articular injection of Bclaf1 shRNA attenuates OA cartilage degradation in mice. Immunoprecipitation, protein mass spectrometry, nuclear translocation assay, siRNA/shRNA knockdown, overexpression, in vivo mouse OA model International journal of biological sciences Medium 39990659
2024 MED23 physically interacts with BCLAF1 in NSCLC cells, as identified by co-IP and mass spectrometry (validated by PLA assays). The MED23/BCLAF1 complex regulates transcription of NUPR1, which controls autophagic flux; loss of MED23 reduces NUPR1 expression and triggers premature senescence. Co-immunoprecipitation, mass spectrometry, proximity ligation assay, RNA-seq, ChIP assay Biochemical and biophysical research communications Medium 39366174
2025 BCKDK phosphorylates BCLAF1 at serine 285, facilitating BCLAF1 binding to the MYC promoter and enhancing MYC transcription in lung cancer cells. Elevated MYC then upregulates hexokinase 2 (HK2), promoting aerobic glycolysis and Trametinib resistance. BCKDK-BCLAF1 interaction was identified through molecular biology experiments. Co-immunoprecipitation, phosphorylation assay (S285 site), ChIP (BCLAF1 at MYC promoter), site-directed mutagenesis, functional glycolysis assays Cell death and differentiation Medium 40442441
2025 Nuclear p85β physically interacts with BCLAF1 and shows genome-wide co-occupancy at gene targets. BCLAF1 recruits p85β to BCLAF1 gene loci, and p85β facilitates assembly of a complex containing BCLAF1, TRIM28, and ZNF263, which together activate BCLAF1 transcription (positive autoregulation). Multi-omics analysis confirmed physical interaction and functional cooperativity. Co-immunoprecipitation, ChIP-seq (co-occupancy), RNA-seq, multi-omics approach Nature communications High 40016211
2025 BCLAF1 physically associates with core spliceosome components and regulates alternative splicing with a predominant effect on intron retention. BCLAF1 is required for productive splicing of ATF4 mRNA to sustain ATF4 protein expression and downstream metabolic gene regulation. Loss of BCLAF1 reduces ATF4 protein levels, disrupts de novo amino acid biosynthesis, and sensitizes AML cells to venetoclax. Co-immunoprecipitation (spliceosome components), RNA-seq/alternative splicing analysis, ATF4 protein/mRNA assays, metabolomics, venetoclax sensitivity assay bioRxiv : the preprint server for biologypreprint Medium 41648520
2025 Bclaf1 undergoes liquid-liquid phase separation (LLPS) to form nuclear biomolecular condensates during oxidative stress in cardiomyocytes. PTK2 sequestered within Bclaf1 condensates is protected from ubiquitin-proteasome-mediated degradation at lysine 926. Disruption of Bclaf1 condensates leads to PTK2 degradation, increased p53 levels, and increased apoptosis. Advanced microscopy (LLPS/condensate visualization), ubiquitination assay, proteasome inhibition, site-directed mutagenesis (K926), Bclaf1 knockdown with apoptosis readout bioRxivpreprint Medium bio_10.1101_2025.02.04.636487
2025 BCLAF1 promotes chromatin accessibility in esophageal carcinoma by activating POLR2A (RNA polymerase II subunit) through two mechanisms: (1) transcriptional activation via co-recruitment of BCLAF1/P300/H3K27ac at the POLR2A super-enhancer (E2/E3 elements), and (2) splicing regulation of pre-POLR2A mRNA through interaction with SNRPA (small nuclear ribonucleoprotein polypeptide A). ATAC-seq (chromatin accessibility), CUT&Tag (co-occupancy at POLR2A super-enhancer), RNA-binding protein immunoprecipitation (RIP) for SNRPA interaction, siRNA knockdown, in vitro and in vivo models Journal of hazardous materials Medium 40220379
2025 BCLAF1 restrains stress response gene expression in hematopoietic stem cells (HSCs) and promotes HSC repopulation activity. BCLAF1 associates with chromatin throughout the genome of fetal and adult hematopoietic cells to regulate transcriptional programs. Loss of BCLAF1 impairs HSC self-renewal and multilineage reconstitution after stem cell transplantation. Hematopoietic-specific and inducible deletion (Cre-lox), single-cell RNA-seq, chromatin association assay, stem cell transplantation/reconstitution assay Blood advances High 40435510

Source papers

Stage 0 corpus · 64 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Btf, a novel death-promoting transcriptional repressor that interacts with Bcl-2-related proteins. Molecular and cellular biology 179 10330179
2014 BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells. Nature communications 152 25091051
2004 Emerin binding to Btf, a death-promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery-Dreifuss muscular dystrophy. European journal of biochemistry 126 15009215
2007 Protein kinase C delta induces transcription of the TP53 tumor suppressor gene by controlling death-promoting factor Btf in the apoptotic response to DNA damage. Molecular and cellular biology 95 17938203
2018 Bclaf1 promotes angiogenesis by regulating HIF-1α transcription in hepatocellular carcinoma. Oncogene 94 30367150
2017 The RNA processing factors THRAP3 and BCLAF1 promote the DNA damage response through selective mRNA splicing and nuclear export. Nucleic acids research 87 29112714
2011 The type III histone deacetylase Sirt1 protein suppresses p300-mediated histone H3 lysine 56 acetylation at Bclaf1 promoter to inhibit T cell activation. The Journal of biological chemistry 82 21454709
2012 BCLAF1 is a radiation-induced H2AX-interacting partner involved in γH2AX-mediated regulation of apoptosis and DNA repair. Cell death & disease 81 22833098
2008 Essential role for Bclaf1 in lung development and immune system function. Cell death and differentiation 71 19008920
2017 miR-194-5p/BCLAF1 deregulation in AML tumorigenesis. Leukemia 67 28216661
2012 BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection. Proceedings of the National Academy of Sciences of the United States of America 66 22645331
2022 Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1-mediated modulation of PI3K/AKT/GSK-3β signaling. Life sciences 60 35882275
2016 Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence. Cell death and differentiation 58 26794446
2010 In search of a function for BCLAF1. TheScientificWorldJournal 56 20661537
2018 Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b. Cell reports 55 29466738
2021 The long noncoding RNA lncCIRBIL disrupts the nuclear translocation of Bclaf1 alleviating cardiac ischemia-reperfusion injury. Nature communications 52 33483496
2019 Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3. PLoS pathogens 52 30682178
2015 Upregulated SMYD3 promotes bladder cancer progression by targeting BCLAF1 and activating autophagy. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 49 26676636
2019 BCLAF1 promotes cell proliferation, invasion and drug-resistance though targeting lncRNA NEAT1 in hepatocellular carcinoma. Life sciences 45 31870774
2009 The proapoptotic C16-ceramide-dependent pathway requires the death-promoting factor Btf in colon adenocarcinoma cells. Journal of proteome research 45 19705920
2022 Exosomal transfer of miR-181b-5p confers senescence-mediated doxorubicin resistance via modulating BCLAF1 in breast cancer. British journal of cancer 39 36522479
2020 Ginsenoside Compound K Regulates HIF-1α-Mediated Glycolysis Through Bclaf1 to Inhibit the Proliferation of Human Liver Cancer Cells. Frontiers in pharmacology 39 33363466
2021 Function of BCLAF1 in human disease. Oncology letters 37 34992690
2020 LncRNA PVT1 accelerates malignant phenotypes of bladder cancer cells by modulating miR-194-5p/BCLAF1 axis as a ceRNA. Aging 33 33188158
2024 BCLAF1 binds SPOP to stabilize PD-L1 and promotes the development and immune escape of hepatocellular carcinoma. Cellular and molecular life sciences : CMLS 29 38340178
2020 Bclaf1 is a direct target of HIF-1 and critically regulates the stability of HIF-1α under hypoxia. Oncogene 23 32029898
2022 Plaque Evaluation by Ultrasound and Transcriptomics Reveals BCLAF1 as a Regulator of Smooth Muscle Cell Lipid Transdifferentiation in Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 22 35321563
2020 BCLAF1 induces cisplatin resistance in lung cancer cells. Oncology letters 21 32968449
2013 Btf and TRAP150 have distinct roles in regulating subcellular mRNA distribution. Nucleus (Austin, Tex.) 21 23778535
2024 CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis. Science China. Life sciences 19 38805063
2018 Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism. Cancer biology & therapy 19 29969367
2024 Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/P53 signaling pathway. Pharmacological research 18 38878918
2019 RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex. Cell reports 18 31644907
2022 TET2-BCLAF1 transcription repression complex epigenetically regulates the expression of colorectal cancer gene Ascl2 via methylation of its promoter. The Journal of biological chemistry 16 35660018
2021 Bclaf1 regulates c-FLIP expression and protects cells from TNF-induced apoptosis and tissue injury. EMBO reports 16 34693625
2019 Structure-Guided Exploration of SDS22 Interactions with Protein Phosphatase PP1 and the Splicing Factor BCLAF1. Structure (London, England : 1993) 16 30661852
2021 Role of BCLAF-1 in PD-L1 stabilization in response to ionizing irradiation. Cancer science 15 34251713
2021 Evaluation of NOx removal from flue gas and Fe(II)EDTA regeneration using a novel BTF-ABR integrated system. Journal of hazardous materials 13 34088200
2024 BCLAF1 drives esophageal squamous cell carcinoma progression through regulation of YTHDF2-dependent SIX1 mRNA degradation. Cancer letters 12 38636894
2025 Targeting the BCKDK/BCLAF1/MYC/HK2 axis to alter aerobic glycolysis and overcome Trametinib resistance in lung cancer. Cell death and differentiation 8 40442441
2022 BCLAF1, a functional partner of BACH1, participates in DNA damage response. DNA repair 7 35930920
2002 Isolation and characterization of BTF-37: chromosomal DNA captured from Bacteroides fragilis that confers self-transferability and expresses a pilus-like structure in Bacteroides spp. and Escherichia coli. Journal of bacteriology 7 11790742
2024 Heparanase interacting BCLAF1 to promote the development and drug resistance of ICC through the PERK/eIF2α pathway. Cancer gene therapy 6 38467765
2023 BCLAF1-induced HIF-1α accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex. Cancer immunology, immunotherapy : CII 6 37906282
2017 Alignment of Mitotic Chromosomes in Human Cells Involves SR-Like Splicing Factors Btf and TRAP150. International journal of molecular sciences 6 28895891
2025 Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction. Cell communication and signaling : CCS 4 39891142
2007 Characterization of BctA, a mating apparatus protein required for transfer of the Bacteroides fragilis conjugal element BTF-37. Research in microbiology 4 17720457
2025 Bclaf1 mediates super-enhancer-driven activation of POLR2A to enhance chromatin accessibility in nitrosamine-induced esophageal carcinogenesis. Journal of hazardous materials 3 40220379
2025 BCLAF1 restrains stress responses in hematopoietic stem cells to support expansion and repopulation. Blood advances 3 40435510
2024 BCLAF1 is Expressed as a Potential Anti-oncogene in Bile Duct Cancer. Biochemical genetics 3 38198022
2023 Identifying and characterising Thrap3, Bclaf1 and Erh interactions using cross-linking mass spectrometry. Wellcome open research 3 35865489
2021 Role of Bclaf1 in Promoting Adrenocortical Carcinoma Proliferation: A Study Combining the Use of Bioinformatics and Molecular Events. Cancer management and research 3 34512018
2025 BCLAF1 Regulates Osteoarthritic Cartilage Degradation Through Interaction with LAMTOR2. International journal of biological sciences 2 39990659
2024 Pan-Cancer Analysis Identifies BCLAF1 as a Potential Biomarker for Renal Cell Carcinoma. Biochemical genetics 2 38573525
2024 Sorbaria sorbifolia flavonoid derivative induces mitochondrial apoptosis in human hepatoma cells through Bclaf1. Frontiers in pharmacology 2 39444606
2021 New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation. Oncology reports 2 34490482
2024 MED23 depletion induces premature senescence in NSCLC cells by interacting with BCLAF1 and then suppressing NUPR1 expression. Biochemical and biophysical research communications 1 39366174
2012 [Characteristics of biofilm phase during the long-term degradation of a toluene-contaminated gas stream using BTF]. Huan jing ke xue= Huanjing kexue 1 23243848
2026 BCLAF1 links RNA splicing to ATF4-dependent metabolic adaptation in acute myeloid leukemia. bioRxiv : the preprint server for biology 0 41648520
2026 Dynamic epigenetic regulation of BCLAF1 splicing in acute myeloid leukemia. Cell death & disease 0 41872140
2026 Huangqi Jianzhong decoction inhibits CRC invasion through the modulation of BCLAF1-mediated glycolysis. Journal of ethnopharmacology 0 42248374
2025 p85β acts as a transcription cofactor and cooperates with BCLAF1 in the nucleus. Nature communications 0 40016211
2025 A novel MIR100HG transcript enhances tumorigenesis by inducing BCLAF1-mediated alternative splicing in colorectal cancer. Cell communication and signaling : CCS 0 40635045
2023 Effects of various COD/NO ratios on NOx removal performance and microbial communities in a BTF-ABR integrated system. Chemosphere 0 36775032

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