Affinage

BCLAF1

Bcl-2-associated transcription factor 1 · UniProt Q9NYF8

Length
920 aa
Mass
106.1 kDa
Annotated
2026-04-28
63 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCLAF1 is a multifunctional nuclear protein that integrates transcriptional regulation, mRNA splicing, and mRNA stability control across diverse cellular processes including apoptosis, the DNA damage response, immune signaling, hypoxic adaptation, and developmental programs. Through its bZIP-like domain, BCLAF1 activates or represses transcription at specific promoters — driving TP53 expression with PKCδ after genotoxic stress (PMID:17938203), CFLAR (c-FLIP) expression with NF-κB p50 to restrain TNF-induced apoptosis (PMID:34693625), HIF1A in a positive feedback loop under hypoxia (PMID:30367150, PMID:32029898), and IL-6/IL-8 with C/EBPβ during therapy-induced senescence (PMID:26794446) — while also forming transcription factor complexes with SPIC to regulate B-cell development (PMID:31644907), with TET2 to control promoter hydroxymethylation (PMID:35660018), and with p85β/TRIM28/ZNF263 in an autoregulatory circuit (PMID:40016211). BCLAF1 additionally associates with spliceosome components and the THRAP3/ERH complex to regulate alternative splicing and nuclear export of transcripts critical for the DNA damage response, mitotic fidelity, and metabolic homeostasis, including ATM kinase and ATF4 mRNAs (PMID:29112714, PMID:35865489), and stabilizes specific mRNAs such as cyclin D1 downstream of the circadian regulator CRY2 (PMID:29466738). Knockout mice reveal requirements for lung smooth muscle morphogenesis and peripheral T-cell homeostasis independent of a simple proapoptotic role, while BCLAF1 also functions as a viral restriction factor neutralized by HCMV and alphaherpesviruses (PMID:19008920, PMID:22645331, PMID:30682178).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1999 High

    The discovery of BCLAF1 established it as a Bcl-2/Bcl-xL-interacting nuclear protein with DNA-binding and transcriptional repression activity whose overexpression induces apoptosis, providing the founding link between anti-apoptotic Bcl-2 family members and a transcription factor.

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

    PMID:10330179

    Open questions at the time
    • Endogenous transcriptional targets unidentified
    • Mechanism of Bcl-2/Bcl-xL cytoplasmic sequestration unclear at molecular level
    • Physiological relevance of proapoptotic activity not tested in vivo
  2. 2004 High

    Identification of emerin as a high-affinity BCLAF1 binding partner, with a disease-causing emerin mutation selectively disrupting this interaction, revealed that BCLAF1 connects to nuclear envelope biology and suggested its subnuclear relocalization during apoptosis.

    Evidence Yeast two-hybrid, biochemical affinity measurement (KD ~100 nM), mutagenesis, immunofluorescence during Fas-induced apoptosis

    PMID:15009215

    Open questions at the time
    • Functional consequence of emerin-BCLAF1 interaction on gene expression undefined
    • Whether BCLAF1 contributes to Emery-Dreifuss muscular dystrophy pathogenesis untested
  3. 2007 High

    Demonstrating that PKCδ partners with BCLAF1 at the TP53 promoter after DNA damage established BCLAF1 as a direct transcriptional activator of a specific endogenous target (TP53), resolving the question of what genes BCLAF1 regulates.

    Evidence ChIP, Co-IP, reporter assays, RNAi knockdown, RT-PCR in genotoxically stressed cells

    PMID:17938203

    Open questions at the time
    • Whether BCLAF1 binds TP53 promoter independently of PKCδ unknown
    • Genome-wide scope of BCLAF1 transcriptional targets not yet mapped
  4. 2008 High

    Bclaf1 knockout mice revealed essential developmental roles in lung morphogenesis and peripheral T-cell homeostasis but no overt apoptosis defect, fundamentally reframing BCLAF1 from a dedicated proapoptotic factor to a pleiotropic regulator.

    Evidence Targeted gene knockout in mice, histology, FACS analysis

    PMID:19008920

    Open questions at the time
    • Molecular targets mediating lung and T-cell phenotypes not identified
    • Conditional tissue-specific knockouts not performed
  5. 2011 High

    Placing BCLAF1 as a Sirt1/NF-κB-regulated downstream effector in T-cell activation explained how BCLAF1 transcription itself is controlled and linked it to chromatin remodeling (H3K56 acetylation) at its own promoter.

    Evidence ChIP for H3K56ac, siRNA epistasis, IL-2 ELISA in Sirt1-null T cells

    PMID:21454709

    Open questions at the time
    • Whether Sirt1-BCLAF1 axis operates outside T cells unclear
    • Downstream BCLAF1 targets in T-cell activation undefined
  6. 2012 High

    Two parallel advances established BCLAF1's roles in DNA damage signaling — promoting γH2AX-associated NHEJ repair via Ku70/DNA-PKcs stabilization — and in antiviral defense, where HCMV evolved two independent strategies (pp71/UL35-mediated degradation and miR-UL112-1 silencing) to neutralize BCLAF1 as a restriction factor.

    Evidence MS-based identification, Co-IP, colocalization with γH2AX, siRNA knockdown for DDR; viral infection assays, proteasome inhibitors, miRNA assays for HCMV

    PMID:22645331 PMID:22833098

    Open questions at the time
    • Whether BCLAF1 participates in HR in addition to NHEJ not addressed
    • Identity of BCLAF1-regulated antiviral genes not determined
    • Structural basis of Ku70/DNA-PKcs stabilization unknown
  7. 2013 Medium

    Localization of BCLAF1 at active transcription loci in an RNA Pol II-dependent manner, overlapping with EJC component Magoh, and the finding that its depletion increases cytoplasmic mRNA levels, established BCLAF1 as a regulator of mRNA subcellular distribution beyond its transcription factor role.

    Evidence Live-cell imaging at reporter loci, nuclear/cytoplasmic fractionation, RT-PCR after siRNA knockdown

    PMID:23778535

    Open questions at the time
    • Whether BCLAF1 directly binds mRNA or acts indirectly through EJC not resolved
    • Specificity of affected transcripts not determined genome-wide
  8. 2014 High

    The demonstration that SRSF10 drives inclusion of BCLAF1 exon 5a to generate an oncogenic isoform in colorectal cancer showed that BCLAF1 function is itself regulated by alternative splicing, adding isoform-level complexity.

    Evidence RT-PCR splicing assays, knockdown/overexpression, tumor growth assays in colon cancer cells and patient samples

    PMID:25091051

    Open questions at the time
    • Functional domain encoded by exon 5a not biochemically characterized
    • Whether other BCLAF1 isoforms have distinct functions unknown
  9. 2016 High

    Identifying BCLAF1 as a bridge between NF-κB and C/EBPβ to drive the senescence-associated secretory phenotype (IL-6/IL-8) established a new cell-fate role for BCLAF1 in therapy-induced senescence.

    Evidence ChIP, Co-IP, reporter assays, IL-6/IL-8 ELISA, xenograft model after doxorubicin treatment

    PMID:26794446

    Open questions at the time
    • Whether BCLAF1 is required for all SASP components or only IL-6/IL-8 unclear
    • Relationship between BCLAF1's senescence and apoptosis roles not delineated
  10. 2017 High

    Multiple studies converged to show BCLAF1 functions as a selective mRNA splicing/export factor for DDR transcripts (including ATM), and as a cofactor for type I interferon signaling through direct STAT2 interaction, broadening its role to RNA processing and innate immunity.

    Evidence RNA-seq splicing analysis, nuclear export assays, DNA damage sensitivity for DDR role; CRISPR/siRNA, Co-IP, ChIP at ISRE elements for IFN role; viral exploitation by alphaherpesvirus US3

    PMID:28895891 PMID:29112714 PMID:30682178

    Open questions at the time
    • Full catalog of BCLAF1-dependent splicing events not defined
    • Mechanism by which BCLAF1 selects specific transcripts for splicing regulation unknown
    • Whether BCLAF1's IFN role extends to type II/III interferons not tested
  11. 2018 High

    Discovery of a HIF-1α/BCLAF1 positive feedback loop under hypoxia — BCLAF1 transcribes HIF1A via its bZIP domain while HIF-1α reciprocally upregulates BCLAF1 — and identification of BCLAF1 as a CRY2-dependent mRNA stabilizer in myogenesis, demonstrated dual transcriptional and post-transcriptional functions in distinct biological contexts.

    Evidence ChIP, reporter assays with bZIP mutants, xenografts for hypoxia; Co-IP, RNA stability assays, Cry2 KO mice for myogenesis

    PMID:29466738 PMID:30367150

    Open questions at the time
    • Direct RNA-binding domains/motifs of BCLAF1 for mRNA stabilization not mapped
    • Whether HIF-1α feedback operates in non-tumor contexts undetermined
  12. 2019 High

    Structural and functional advances revealed that BCLAF1 forms a transcription factor complex with SPIC to displace PU.1 genome-wide during B-cell development, and that phosphorylated BCLAF1 binds the PP1/SDS22 phosphatase complex, identifying post-translational regulation of BCLAF1.

    Evidence ChIP-seq, Co-IP, genetic epistasis in pre-B cells for SPIC complex; X-ray crystallography of SDS22, biochemical binding for PP1

    PMID:30661852 PMID:31644907

    Open questions at the time
    • Which phosphorylation sites on BCLAF1 are regulated by PP1/SDS22 undefined
    • Whether SPIC/BCLAF1 complex operates outside B cells unclear
  13. 2020 High

    CRISPR knockout confirmed BCLAF1 stabilizes HIF-1α protein in the nucleus during sustained hypoxia, validating the positive feedback loop with genetic loss-of-function and in vivo xenograft evidence.

    Evidence CRISPR knockout, Co-IP, protein stability assays, xenograft tumor growth measurement

    PMID:32029898

    Open questions at the time
    • Structural mechanism of HIF-1α stabilization by BCLAF1 unresolved
    • Whether BCLAF1 protects HIF-1α from VHL-mediated or VHL-independent degradation not distinguished
  14. 2021 High

    Two studies resolved context-dependent pro- vs anti-apoptotic roles: BCLAF1 promotes cardiomyocyte apoptosis after ischemia-reperfusion (sequestered by lncCIRBIL), while in TNF signaling it prevents apoptosis by activating CFLAR/c-FLIP transcription via NF-κB p50, explaining the long-standing paradox of its dual roles.

    Evidence Transgenic/KO mouse epistasis for cardiac I/R; Co-IP, ChIP at CFLAR promoter, TNF-induced apoptosis assays, in vivo siRNA for TNF pathway

    PMID:33483496 PMID:34693625

    Open questions at the time
    • What determines pro- vs anti-apoptotic output in a given cell type not defined
    • Post-translational modifications dictating context-dependent function not mapped systematically
  15. 2022 High

    Identification of BCLAF1 as a competitive inhibitor of SPOP-mediated PD-L1 ubiquitination through a defined SBC motif, and as a TET2 partner regulating promoter hydroxymethylation, expanded BCLAF1 into immune checkpoint regulation and epigenetic control.

    Evidence Site-directed mutagenesis of SBC motif, ubiquitination competition assay, T-cell cytotoxicity for SPOP/PD-L1; LC-MS/MS, PLA, ChIP-qPCR, glucosylated hydroxymethyl-qPCR for TET2

    PMID:35660018 PMID:38340178

    Open questions at the time
    • In vivo relevance of BCLAF1-SPOP axis for anti-tumor immunity not tested
    • Genome-wide scope of TET2-BCLAF1 hydroxymethylation targets unknown
  16. 2023 Medium

    Cross-linking mass spectrometry defined the BCLAF1-THRAP3-ERH (TEB) complex topology, mapping interaction surfaces to ordered regions within these largely disordered proteins and suggesting a stable ternary complex as the functional unit for RNA processing.

    Evidence XL-MS with DSSO crosslinker after immunoprecipitation of endogenous proteins

    PMID:35865489

    Open questions at the time
    • Functional validation of TEB complex as a unit is absent
    • No reconstitution or structural model beyond crosslink restraints
    • Stoichiometry and dynamics of the complex unknown
  17. 2024 Medium

    Multiple studies expanded the BCLAF1 interaction network: BACH1/BRCA1-dependent recruitment to DNA damage sites for homologous recombination, YTHDF2 antagonism to stabilize m6A-modified mRNAs, LAMTOR2-regulated nuclear translocation, and MED23 partnership for NUPR1 transcription, each linking BCLAF1 to additional pathways.

    Evidence Tandem affinity purification and HR reporter for BACH1; MS, Co-IP, GST pull-down, MeRIP-seq for YTHDF2; Co-IP, fractionation, OA mouse model for LAMTOR2; Co-IP, PLA, ChIP for MED23

    PMID:35930920 PMID:38636894 PMID:39366174 PMID:39990659

    Open questions at the time
    • Mechanism by which BCLAF1 participates in HR downstream of RAD51 foci undefined
    • Whether BCLAF1-YTHDF2 interaction is direct and stoichiometric needs further validation
    • Selectivity of LAMTOR2 regulation of BCLAF1 nuclear entry unclear
  18. 2025 Medium

    Recent work revealed that nuclear p85β recruits BCLAF1 into an autoregulatory transcriptional loop with TRIM28/ZNF263, BCKDK phosphorylates BCLAF1 at S285 to promote MYC transcription and glycolysis, and BCLAF1 activates POLR2A through dual transcriptional and splicing mechanisms — collectively demonstrating that BCLAF1 is itself a hub for multiple upstream kinase and cofactor inputs.

    Evidence ChIP-seq/proteomics for p85β; Co-IP, S285 phosphorylation, ChIP at MYC promoter for BCKDK; ATAC-seq, CUT&Tag, RIP for POLR2A regulation

    PMID:40016211 PMID:40220379 PMID:40442441

    Open questions at the time
    • Whether S285 phosphorylation by BCKDK occurs in non-cancer contexts not known
    • Complete phosphoproteome map of BCLAF1 lacking
    • Whether POLR2A regulation is a direct or indirect consequence of BCLAF1's general splicing role unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive structural model of full-length BCLAF1, the rules governing its context-dependent switch between pro- and anti-apoptotic outputs, and the relative contributions of its transcriptional versus RNA-processing functions in each physiological setting remain to be established.
  • No high-resolution structure of full-length BCLAF1 or its key domains beyond bZIP homology
  • Systematic mapping of post-translational modifications and their functional consequences incomplete
  • No unified model explaining how one protein integrates transcription, splicing, and mRNA stability in a context-dependent manner

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003723 RNA binding 5 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 10 GO:0005654 nucleoplasm 4 GO:0005694 chromosome 2
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-5357801 Programmed Cell Death 5 R-HSA-8953854 Metabolism of RNA 5 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-1266738 Developmental Biology 2 R-HSA-4839726 Chromatin organization 2 R-HSA-1640170 Cell Cycle 1
Partners
BACH1CRY2HIF1ANFKB1SPICSPOPSTAT2THRAP3
Complex memberships
BCLAF1-THRAP3-ERH (TEB) complexSPIC-BCLAF1 transcription factor complexTET2-BCLAF1 complexp85β-BCLAF1-TRIM28-ZNF263 complex

Evidence

Reading pass · 34 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 the antiapoptotic proteins E1B 19K, Bcl-2, and Bcl-xL (but not proapoptotic Bax) via yeast two-hybrid screening. Btf contains homology to bZIP and Myb DNA-binding domains, 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, in vitro DNA binding, reporter transcription assays, overexpression/apoptosis assays Molecular and cellular biology High 10330179
2004 Emerin (a nuclear membrane protein mutated in Emery-Dreifuss muscular dystrophy) directly binds BCLAF1/Btf with KD ~100 nM. The emerin disease-causing missense mutation S54F selectively disrupts binding to Btf without affecting binding to lamin A or GCL. Upon Fas-induced apoptosis, Btf redistributes from dot-like nuclear structures to a zone near the nuclear envelope, suggesting apoptotic regulation of Btf localization. Yeast two-hybrid, biochemical binding/affinity measurement, alanine-substitution mutagenesis, indirect immunofluorescence European journal of biochemistry High 15009215
2007 PKCδ interacts with BCLAF1/Btf upon DNA damage and co-occupies the TP53 core promoter element (CPE-TP53), driving TP53 transcription. Inhibition of PKCδ activity reduces Btf affinity for CPE-TP53, lowering TP53 mRNA and protein levels. RNAi-mediated disruption of Btf-mediated TP53 transcription suppresses TP53-dependent apoptosis after genotoxic stress. Reporter assays, Co-IP, ChIP, RNAi knockdown, RT-PCR, Western blot Molecular and cellular biology High 17938203
2008 Bclaf1 knockout mice show defects in lung saccular-stage smooth muscle organization and peripheral T-cell homeostasis, but not thymocyte development. Bclaf1-deficient cells do not show defects in apoptosis after various stimuli, indicating Bclaf1 is required for developmental processes independent of its postulated proapoptotic role. Targeted gene knockout in mice, histology, FACS analysis of immune cells Cell death and differentiation High 19008920
2011 Sirt1 suppresses BCLAF1 transcription by deacetylating histone H3 lysine 56 (H3K56) at the bclaf1 promoter. Upon TCR/CD28 stimulation, Sirt1 is recruited to the bclaf1 promoter by forming a complex with p300 and NF-κB subunit Rel-A; only p300 (not GCN5) specifically acetylates H3K56 at this promoter. Knockdown of Bclaf1 suppresses hyperactivation of Sirt1-null T cells, placing Bclaf1 downstream of Sirt1 in T cell activation. ChIP, siRNA knockdown, H3K56 acetylation assay, IL-2 ELISA, proliferation assay The Journal of biological chemistry High 21454709
2012 BCLAF1 associates with γH2AX in a radiation dose-dependent manner. Under high-dose ionizing radiation, BCLAF1 promotes apoptosis by disrupting p21-mediated inhibition of caspase/cyclin E-dependent mitochondrial pathways and co-localizes with γH2AX foci while stabilizing the Ku70/DNA-PKcs complex to facilitate NHEJ-based DSB repair in surviving cells. In tumor cells, BCLAF1 is suppressed, leading to anti-apoptotic Ku70-Bax complexes and defective NHEJ repair. Mass spectrometry-based identification, Co-IP, immunofluorescence colocalization, siRNA knockdown, apoptosis assays Cell death & disease High 22833098
2012 Human cytomegalovirus uses two independent mechanisms to neutralize BCLAF1 as a restriction factor: (1) virion-delivered pp71 and UL35 proteins direct proteasomal degradation of BCLAF1 immediately post-infection; (2) virus-encoded miR-UL112-1 downregulates BCLAF1 at late infection stages. In the absence of BCLAF1 neutralization, viral gene expression and replication are inhibited. Viral infection assays, siRNA knockdown, proteasome inhibitor treatment, miRNA functional assays Proceedings of the National Academy of Sciences of the United States of America High 22645331
2013 Btf (BCLAF1) and TRAP150 both localize at active transcription loci in a RNA polymerase II-dependent manner and overlap with the exon junction complex (EJC) protein Magoh. Btf depletion (but not TRAP150 depletion) causes increased cytoplasmic levels of β-tropomyosin reporter transcripts and global increase of endogenous polyadenylated RNA in the cytoplasm, indicating a distinct role for Btf in regulating subcellular mRNA distribution. Live-cell imaging at reporter loci, siRNA knockdown, nuclear/cytoplasmic fractionation, RT-PCR Nucleus (Austin, Tex.) Medium 23778535
2014 The splicing factor SRSF10 stimulates inclusion of BCLAF1 alternative exon 5a, generating a distinct protein isoform. The BCLAF1 isoform resulting from exon 5a inclusion promotes growth and tumorigenic potential of colon cancer cells, while its knockdown inhibits these effects. SRSF10 upregulation in colorectal cancer parallels increased exon 5a inclusion, linking SRSF10-regulated splicing to BCLAF1 oncogenic isoform production. RT-PCR splicing assays, siRNA knockdown, overexpression, tumor growth assays Nature communications High 25091051
2016 Bclaf1 is upregulated through the ATM/Nemo/NF-κB pathway during doxorubicin-induced senescence and is a direct transcriptional target of p65 and c-Rel. Bclaf1 physically interacts with the leucine zipper region of C/EBPβ and together they upregulate IL-6 and IL-8 transcription to establish the senescence-associated secretory phenotype (SASP). Bclaf1 is thus an NF-κB-to-C/EBPβ transducer in therapy-induced senescence. ChIP, Co-IP, siRNA knockdown, reporter assays, IL-6/IL-8 ELISA, xenograft model Cell death and differentiation High 26794446
2017 THRAP3 and BCLAF1 promote the DNA damage response by selectively regulating mRNA splicing and nuclear export of key DDR transcripts, including ATM kinase mRNA. Loss of either protein leads to sensitivity to DNA damaging agents, defective DNA repair, and genomic instability. Cancer-associated mutations in THRAP3 deregulate THRAP3/BCLAF1-controlled transcript processing. siRNA knockdown, RNA-seq splicing analysis, nuclear export assays, DNA damage sensitivity assays, comet assay Nucleic acids research High 29112714
2017 Bclaf1 is required for type I interferon (IFNα) signaling: Bclaf1 maintains efficient STAT1 and STAT2 phosphorylation in response to IFNα, directly interacts with ISRE elements and STAT2 to facilitate ISGF3 binding for gene transcription. Alphaherpesvirus US3 protein degrades Bclaf1 to impair IFNα-mediated antiviral defense. CRISPR/siRNA knockdown, Co-IP, ChIP, STAT phosphorylation assays, viral replication assays PLoS pathogens High 30682178
2018 Bclaf1 promotes HIF1A transcription via its bZIP domain in hepatocellular carcinoma cells under hypoxia, leading to increased downstream VEGFA, TGFB, and EPO expression and angiogenesis. Conversely, HIF-1α increases Bclaf1 levels in hypoxia, forming a positive feedback loop. Bclaf1 knockdown in xenograft tumors reduces HIF-1α levels and microvessel density. shRNA knockdown, reporter assays with bZIP domain mutants, Western blot, xenograft experiments, ChIP Oncogene High 30367150
2018 Cry2 interacts specifically with Bclaf1 (not Cry1), and this interaction stabilizes mRNAs encoding cyclin D1 and Tmem176b in myoblasts. Loss of Cry2 or Bclaf1 knockdown recapitulates the same phenotype: premature cell cycle exit and inefficient myotube fusion. Bclaf1 thus acts as a post-transcriptional mRNA stabilizer downstream of the circadian regulator Cry2. Co-IP, RNA stability assays, siRNA knockdown, cell fusion assays, Cry2 KO mice, muscle regeneration assays Cell reports High 29466738
2019 A SPIC/BCLAF1 transcription factor complex is activated by RAG-generated DNA double-strand breaks in pre-B cells. SPIC recruits BCLAF1 to gene-regulatory elements, and the complex displaces PU.1 from chromatin genome-wide and suppresses SYK tyrosine kinase expression, enforcing the transition from large to small pre-B cells. ChIP-seq, Co-IP, genetic loss-of-function, gene expression profiling, B cell development assays Cell reports High 31644907
2019 Crystal structure of SDS22 shows its leucine-rich repeat domain adopts a banana-shaped fold with a large basic surface patch that enables binding of a phosphorylated form of BCLAF1. Biochemical studies show SDS22 acts as a 'third' subunit of multiple PP1 holoenzymes and recruits additional interactors such as phosphorylated BCLAF1. X-ray crystallography, biochemical binding studies Structure (London, England : 1993) High 30661852
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 stabilizes HIF-1α protein during long-term hypoxia, protecting it from degradation. Bclaf1 knockout cells show reduced HIF-1α stability and impaired HIF-1 target gene induction; Bclaf1 knockout xenografts show reduced tumor growth with decreased HIF-1α. ChIP, Co-IP, protein stability assays, CRISPR knockout, xenograft experiments Oncogene High 32029898
2021 The long noncoding RNA lncCIRBIL directly binds to Bclaf1 and inhibits its nuclear translocation. Cardiomyocyte-specific transgenic overexpression of lncCIRBIL reduces cardiac infarct area after ischemia-reperfusion (I/R) injury, while Bclaf1 transgenic overexpression worsens I/R injury. Partial Bclaf1 knockout abrogates the detrimental effects of lncCIRBIL knockout, placing Bclaf1 downstream of lncCIRBIL in cardiac I/R injury. RNA-protein binding assay, nuclear fractionation, transgenic mouse models, Bclaf1 KO, infarct area measurement Nature communications High 33483496
2021 Bclaf1 exerts anti-apoptotic function in TNF signaling by promoting transcription of CFLAR (c-FLIP), a caspase-8 antagonist. Bclaf1 binds the p50 subunit of NF-κB, and this interaction is required for Bclaf1 to stimulate CFLAR transcription. Bclaf1 depletion sensitizes cells to TNF-induced apoptosis but not necroptosis, and in mice, siRNA-mediated Bclaf1 depletion aggravates TNF-induced intestinal injury. Co-IP, ChIP, siRNA knockdown, apoptosis/necroptosis assays, in vivo siRNA administration EMBO reports High 34693625
2022 BCLAF1 interacts with SPOP (an E3 ligase adaptor) through an SPOP-binding consensus (SBC) motif on BCLAF1, competitively inhibiting SPOP-mediated ubiquitination and degradation of PD-L1. Mutation of the BCLAF1-SBC motif disrupts BCLAF1-SPOP interaction and abolishes BCLAF1-mediated PD-L1 stabilization. BCLAF1 depletion reduces PD-L1 expression and promotes T cell-mediated cytotoxicity. Co-IP, site-directed mutagenesis (SBC motif), ubiquitination assay, PD-L1 stability assay, T cell co-culture cytotoxicity Cellular and molecular life sciences : CMLS High 38340178
2022 TET2 and BCLAF1 form a transcription repression complex in colorectal cancer cells, identified by LC-MS/MS, co-IP, immunofluorescence colocalization, and proximity ligation assays. The TET2-BCLAF1 complex binds to the Ascl2 promoter and restrains its hypermethylation by inducing hydroxymethylation at CCGG sites, regulating Ascl2-dependent stem gene expression. LC-MS/MS, Co-IP, immunofluorescence colocalization, PLA, ChIP-qPCR, glucosylated hydroxymethyl-sensitive qPCR The Journal of biological chemistry High 35660018
2022 BCLAF1 regulates smooth muscle cell (SMC) survival and lipid transdifferentiation in atherosclerosis. BCLAF1 silencing leads to downregulation of BCL2 and SMC markers, reduced proliferation, and increased apoptosis. BCLAF1 interacts with BCL2 by proximity ligation assay in CD68+ cells of SMC origin in plaques. BCLAF1 knockdown prevents oxLDL-induced SMC transdifferentiation to macrophage-like phenotype. siRNA knockdown, proximity ligation assay, immunohistochemistry, MYH11 lineage-tracing atherosclerotic mice Arteriosclerosis, thrombosis, and vascular biology Medium 35321563
2023 Cross-linking mass spectrometry (XL-MS) of endogenous proteins revealed that Bclaf1, Thrap3, and Erh interact closely with each other, with interaction surfaces mapped to non-disordered portions of these largely disordered proteins, suggesting they form a novel TEB complex. Cross-linking mass spectrometry (XL-MS) with DSSO crosslinker after immunoprecipitation of endogenous proteins Wellcome open research Medium 35865489
2023 BCLAF1 interacts with Cullin 3 (CUL3), and through this interaction BCLAF1 promotes ubiquitination and degradation of PHD2 (prolyl hydroxylase domain protein 2), leading to HIF-1α accumulation under normoxic conditions and upregulation of PD-L1 transcription. Co-IP, immunofluorescence, Western blot, RT-qPCR, ubiquitination assay Cancer immunology, immunotherapy : CII Medium 37906282
2024 BCLAF1 interacts with YTHDF2 (an m6A reader protein) in esophageal squamous cell carcinoma, as identified by mass spectrometry, co-immunoprecipitation, and GST pull-down. BCLAF1 reduces YTHDF2 tumor-suppressive activity, and this promotes SIX1 mRNA stability and expression (via reduced m6A-dependent degradation), enhancing glycolysis and cancer progression. Mass spectrometry, Co-IP, GST pull-down, MeRIP-seq, RIP-seq, transcriptomic analysis Cancer letters High 38636894
2024 BCLAF1 interacts with BACH1 (BRCA1-associated C-terminal helicase) constitutively; upon DNA damage, BCLAF1 is recruited to DNA damage sites in a BACH1- and BRCA1-dependent manner. BCLAF1-deficient cells are defective in DSB-initiated homologous recombination (HR), although RAD51 foci formation is intact. Tandem protein affinity purification, Co-IP, immunofluorescence (DNA damage foci), siRNA knockdown, HR reporter assay DNA repair Medium 35930920
2024 BCLAF1 interacts with LAMTOR2, and this interaction regulates the nuclear translocation of BCLAF1. In osteoarthritis, BCLAF1 is upregulated in chondrocytes and promotes catabolic gene expression and apoptosis; BCLAF1 knockdown via intra-articular adeno-associated virus attenuates cartilage degradation in vivo. Co-IP, mass spectrometry, subcellular fractionation, adenoviral shRNA in vivo, OA mouse model International journal of biological sciences Medium 39990659
2024 MED23 (a mediator complex subunit) interacts with BCLAF1, and this MED23/BCLAF1 complex regulates NUPR1 transcription in NSCLC cells. Loss of MED23 triggers premature senescence through disrupted autophagic flux dependent on NUPR1 expression downstream of the complex. Co-IP, mass spectrometry, PLA, RNA-seq, ChIP assay Biochemical and biophysical research communications Medium 39366174
2025 Nuclear p85β (regulatory subunit of PI3K) physically interacts with BCLAF1 and co-occupies gene loci genome-wide. BCLAF1 recruits p85β to BCLAF1 gene loci, and p85β facilitates assembly of BCLAF1, TRIM28, and ZNF263 to activate BCLAF1 transcription in a positive autoregulatory loop. This nuclear function of p85β/BCLAF1 contributes to oncogenic gene transcription. Multi-omics (ChIP-seq, proteomics), Co-IP, knockdown, reporter assays 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, thereby sustaining ATF4 protein expression. Loss of BCLAF1 reduces ATF4 protein levels, downregulates metabolic target genes, disrupts de novo amino acid biosynthesis, and sensitizes AML cells to venetoclax. Co-IP (spliceosome components), RNA-seq splicing analysis, BCLAF1 depletion, ATF4 protein/mRNA analysis, metabolic assays, drug sensitivity assay bioRxivpreprint Medium 41648520
2025 Bclaf1 undergoes liquid-liquid phase separation (LLPS) in cardiomyocytes under oxidative stress, forming biomolecular condensates in the nucleus that sequester PTK2 (FAK). PTK2 within Bclaf1 condensates is protected from ubiquitin-proteasome system (UPS)-mediated degradation at the K926 ubiquitination site. Disruption of Bclaf1 condensates leads to PTK2 degradation, increased p53 levels, and apoptosis. Advanced fluorescence microscopy (LLPS visualization), Co-IP, ubiquitination site mapping (K926), proteasome inhibition, Bclaf1 knockdown bioRxivpreprint Low bio_10.1101_2025.02.04.636487
2025 BCKDK (branched-chain ketoacid dehydrogenase kinase) interacts with BCLAF1 and promotes its phosphorylation at serine 285, which facilitates BCLAF1 binding to the MYC promoter to enhance MYC transcription, driving HK2-dependent aerobic glycolysis and Trametinib resistance in lung cancer. Co-IP, phosphorylation assay (S285 site), ChIP at MYC promoter, BCKDK/BCLAF1 knockdown, glycolysis assay Cell death and differentiation Medium 40442441
2017 Depletion of Btf (BCLAF1) and/or TRAP150 causes mitotic chromosome misalignment defects in human cells, associated with altered abundance of transcripts encoding mitotic checkpoint regulators, indicating BCLAF1 controls mitotic progression through regulating mitotic regulator mRNA levels. siRNA knockdown, live-cell microscopy, RT-PCR for mitotic regulator transcripts International journal of molecular sciences Medium 28895891
2025 Bclaf1 promotes chromatin accessibility in esophageal carcinogenesis by activating POLR2A (RNA polymerase II subunit) through two mechanisms: (1) transcriptionally, Bclaf1/P300/H3K27ac co-recruitment at the POLR2A super-enhancer (E2/E3 elements) drives transcription; (2) post-transcriptionally, Bclaf1 cofactor SNRPA interacts with pre-POLR2A mRNA to regulate its splicing. ATAC-seq, CUT&Tag, RIP assay, ChIP, siRNA knockdown, ATAC-seq after Bclaf1 silencing Journal of hazardous materials Medium 40220379

Source papers

Stage 0 corpus · 63 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 150 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 125 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 93 30367150
2017 The RNA processing factors THRAP3 and BCLAF1 promote the DNA damage response through selective mRNA splicing and nuclear export. Nucleic acids research 86 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 66 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
2016 Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence. Cell death and differentiation 58 26794446
2022 Curcumin induces mitochondrial apoptosis in human hepatoma cells through BCLAF1-mediated modulation of PI3K/AKT/GSK-3β signaling. Life sciences 57 35882275
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 53 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 51 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
2020 Ginsenoside Compound K Regulates HIF-1α-Mediated Glycolysis Through Bclaf1 to Inhibit the Proliferation of Human Liver Cancer Cells. Frontiers in pharmacology 37 33363466
2022 Exosomal transfer of miR-181b-5p confers senescence-mediated doxorubicin resistance via modulating BCLAF1 in breast cancer. British journal of cancer 36 36522479
2021 Function of BCLAF1 in human disease. Oncology letters 35 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 28 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
2013 Btf and TRAP150 have distinct roles in regulating subcellular mRNA distribution. Nucleus (Austin, Tex.) 21 23778535
2020 BCLAF1 induces cisplatin resistance in lung cancer cells. Oncology letters 20 32968449
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
2019 RAG-Mediated DNA Breaks Attenuate PU.1 Activity in Early B Cells through Activation of a SPIC-BCLAF1 Complex. Cell reports 17 31644907
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
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 15 38878918
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 15 35660018
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
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 Targeting the BCKDK/BCLAF1/MYC/HK2 axis to alter aerobic glycolysis and overcome Trametinib resistance in lung cancer. Cell death and differentiation 5 40442441
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 Ionizing radiation-induced disruption of Rela-Bclaf1-spliceosome regulatory axis in primary spermatocytes causing spermatogenesis dysfunction. Cell communication and signaling : CCS 3 39891142
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
2024 Pan-Cancer Analysis Identifies BCLAF1 as a Potential Biomarker for Renal Cell Carcinoma. Biochemical genetics 2 38573525
2021 New insights from Whole Genome Sequencing: BCLAF1 deletion as a structural variant that predisposes cells towards cellular transformation. Oncology reports 2 34490482
2025 BCLAF1 Regulates Osteoarthritic Cartilage Degradation Through Interaction with LAMTOR2. International journal of biological sciences 1 39990659
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
2024 Sorbaria sorbifolia flavonoid derivative induces mitochondrial apoptosis in human hepatoma cells through Bclaf1. Frontiers in pharmacology 1 39444606
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
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