Affinage

BMF

Bcl-2-modifying factor · UniProt Q96LC9

Length
184 aa
Mass
20.5 kDa
Annotated
2026-06-09
78 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMF is a BH3-only proapoptotic member of the Bcl-2 family that couples cytoskeletal integrity and diverse stress signals to the intrinsic (mitochondrial) apoptosis pathway (PMID:11546872, PMID:21673109). In healthy cells it is held inactive at the cytoskeleton through binding of its conserved motif to dynein light chain 2 (DLC2/DYNLL2) on myosin V motors, and loss of cell attachment (anoikis) or actin disruption releases BMF to engage prosurvival Bcl-2 proteins (PMID:11546872, PMID:17360431). Release is controlled by direct phosphorylation: p38 MAPK phosphorylates Thr72, a residue that crystallography shows directly contacts DLC2, so that phosphorylation sterically blocks the BMF/DLC2 interface and frees BMF (PMID:34462553); JNK-mediated Ser74 phosphorylation modestly enhances activity, while ERK2 phosphorylation of Ser77 is inhibitory and acts without altering localization or partner binding (PMID:19841067, PMID:22258404). BMF is intrinsically disordered, and only its BH3 element folds into an α-helix upon binding the canonical groove of prosurvival proteins, engaging Bcl-2 and Bcl-xL with high affinity and Mcl-1 weakly owing to a missing Asp-Arg salt bridge (PMID:16645638, PMID:37560128); through this neutralization BMF promotes Bax/Bak activation, functioning largely by inhibiting antiapoptotic proteins and by competitively displacing other BH3-only proteins such as Bim (PMID:20431602, PMID:23991648). Genetically, BMF is required for developmental and stress-induced apoptosis in vivo—B-cell homeostasis, lymphocyte sensitivity to glucocorticoids and HDAC inhibitors, intestinal epithelial anoikis, primordial follicle depletion, and uterovaginal development—and acts as a tumor suppressor, including in c-Myc-driven lymphomagenesis via a p53-independent pathway (PMID:18299399, PMID:19841067, PMID:21673109, PMID:19965635, PMID:28771225). BMF transcription integrates numerous inputs, being activated by FOXO3, Smad4-dependent TGF-β signaling, AMPK energy stress, and histone hyperacetylation, and repressed by oncogenic MEK/ERK and PI3K/AKT signaling, FOXM1, c-Myc, mutant p53, and HDAC-containing repressor complexes (HDAC8/STAT3, DNTTIP1/MiDAC, Kaiso/HDAC1) (PMID:17360431, PMID:16909112, PMID:25321483, PMID:20841353, PMID:27035620, PMID:41603084). Stability and isoform usage add further control: DYNLL-induced oligomerization protects BMF from ubiquitin-independent 20S proteasomal degradation, alternative CUG-initiated translation and splicing generate isoforms with differing apoptotic capacity, and RBMS2 stabilizes BMF mRNA (PMID:20706276, PMID:14574334, PMID:31189926, PMID:35280673). Beyond apoptosis, suppression of BMF reduces Beclin-1/Bcl-2 sequestration and thereby facilitates autophagy (PMID:23629966).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Established BMF's defining mechanism: a BH3-only protein sequestered on the cytoskeleton that is released by loss of attachment to trigger apoptosis, answering how cytoskeletal status is sensed by the apoptotic machinery.

    Evidence Co-IP, subcellular fractionation, domain mutagenesis and overexpression apoptosis assays defining DLC2/myosin V anchoring and BH3-dependent killing

    PMID:11546872

    Open questions at the time
    • Did not define the molecular trigger that releases BMF from DLC2
    • Affinities for individual prosurvival proteins not quantified
  2. 2004 Medium

    Showed BMF function is shaped by alternative splicing, identifying isoforms lacking the BH3 domain that are non-apoptotic and even pro-proliferative.

    Evidence cDNA cloning of Bmf-II/III from B-CLL cells with overexpression apoptosis and colony formation assays

    PMID:14574334

    Open questions at the time
    • Physiological abundance and regulation of these isoforms not established
    • Single-lab overexpression-based characterization
  3. 2006 High

    Explained the structural basis of BMF action: it is intrinsically disordered and its BH3 element folds only upon binding prosurvival partners (coupled folding and binding).

    Evidence NMR spectroscopy, circular dichroism and sequence analysis of BMF/Bim/Bad

    PMID:16645638

    Open questions at the time
    • Did not provide complex structures or partner-specific binding determinants
  4. 2006 High

    Connected upstream cytokine and chromatin inputs to BMF transcription, showing TGF-β (Smad4/p38/ROS) and HDAC inhibitors induce BMF to drive apoptosis.

    Evidence siRNA knockdown, Smad4-null cells, pathway inhibitors and ChIP showing promoter histone hyperacetylation

    PMID:15947789 PMID:16909112

    Open questions at the time
    • Direct transcription factors at the promoter not fully resolved
    • Relative contribution of BMF vs Bim varies by stimulus
  5. 2007 High

    Defined BMF as a transcriptionally controlled effector of anoikis and luminal clearance, specifically responsive to matrix detachment and actin disruption.

    Evidence Microarray, siRNA knockdown and 3D mammary acinar morphogenesis with MEK/PI3K pathway manipulation

    PMID:17360431

    Open questions at the time
    • Transcription factor mediating detachment-induced BMF not identified here
  6. 2008 High

    Provided in vivo proof of BMF's apoptotic and tumor-suppressor roles, restricting B-cell survival and constraining lymphomagenesis.

    Evidence Bmf knockout mice with defined apoptotic stimuli and γ-irradiation lymphoma model

    PMID:18299399

    Open questions at the time
    • Stimulus selectivity (glucocorticoid/HDACi but not anoikis/UV in lymphocytes) mechanistically unexplained
  7. 2009 High

    Identified the kinase logic of BMF release and partner engagement, showing MEK inhibition drives cytoskeleton-to-cytosol translocation requiring both DLC2 dissociation and an intact BH3 domain, and that c-Myc represses BMF in a p53-independent tumor-suppressor circuit.

    Evidence Fractionation, immunofluorescence, A69P/L138A mutants and MEK inhibitors; Eμ-myc/bmf compound mice

    PMID:19244105 PMID:19965635

    Open questions at the time
    • Direct kinase acting on the DLC2 interface not yet identified at this stage
    • Mechanism of c-Myc repression of the BMF promoter not detailed
  8. 2010 High

    Mapped diverse stress inputs and phosphoregulatory fine-tuning of BMF, including JNK-dependent release, JNK Ser74 activation, energy stress via AMPK, hypoxia/HIF suppression, CUG-initiated isoforms, and BMF-mediated displacement of Bim during chemotherapy.

    Evidence siRNA screens, fractionation, Ser74 phospho-mutant knock-in and compound Bim/Bmf knockout mice, AMPK pharmacology, 3D culture, CUG mutagenesis, and reciprocal Co-IP/BH3 profiling

    PMID:19300516 PMID:19841067 PMID:20431602 PMID:20706276 PMID:20841353 PMID:20861305

    Open questions at the time
    • Hierarchy and combinatorial integration of these inputs unresolved
    • In vivo relevance of CUG isoforms not established
  9. 2011 High

    Confirmed BMF as a mitochondrial relay of cytoskeletal damage in primary human epithelium, localizing to mitochondria upon detachment to drive caspase-3 activation.

    Evidence Bmf-deficient mice, primary human IEC fractionation, siRNA knockdown and caspase-3 assays

    PMID:21673109

    Open questions at the time
    • Did not resolve how cytoskeletal signal is biochemically transmitted to BMF in IECs
  10. 2012 High

    Defined ERK2 as a direct inhibitory kinase, phosphorylating Ser77 to dampen BMF killing without changing localization or partner binding.

    Evidence In vitro ERK2 kinase assay, phospho-specific antibodies, Ser77 mutants and Co-IP

    PMID:22258404

    Open questions at the time
    • Mechanism by which Ser77 phosphorylation reduces activity remains undefined
  11. 2013 High

    Linked BMF to autophagy regulation and tested the indirect-activation model, showing IFN-γ/p53-HDAC1 suppression of BMF relieves Beclin-1/Bcl-2 sequestration, and that BMF requires antiapoptotic targets to kill.

    Evidence ChIP, p53-HDAC1 Co-IP, bmf-null cells with autophagy readouts; yeast reconstitution with defined Bcl-2 family combinations

    PMID:23629966 PMID:23991648

    Open questions at the time
    • Indirect-activation conclusion drawn in yeast only
    • Whether BMF can directly activate Bax/Bak in mammals unresolved
  12. 2014 High

    Resolved a chromatin repressor mechanism controlling BMF, with HDAC8 governing STAT3/Sp3-versus-p300 exchange at the promoter.

    Evidence ChIP, HDAC8/STAT3 knockdown, p300 inhibition and HDAC8 overexpression

    PMID:25321483

    Open questions at the time
    • Upstream signals selecting STAT3 versus p300 occupancy not defined
  13. 2015 Medium

    Showed oncogenic suppression of BMF confers anoikis resistance, with mutant p53-R273H and PI3K/AKT signaling silencing BMF.

    Evidence Allele-specific p53-R273H knockdown, AKT phosphorylation analysis, suspension anoikis assays and PI3K inhibition

    PMID:26181206

    Open questions at the time
    • Direct vs indirect repression of BMF promoter by mutant p53 not distinguished
  14. 2016 High

    Identified FOXO3 as a direct activating transcription factor and a CLL-susceptibility enhancer variant, linking BMF regulation to metastasis and disease risk.

    Evidence ChIP for FOXO3 at the BMF promoter, xenograft rescue, and super-enhancer SNP analysis disrupting RELA binding

    PMID:27035620 PMID:27524613

    Open questions at the time
    • Interplay between FOXO3 and RELA enhancer inputs not integrated
    • RELA SNP effect shown by reporter/allele-specific assays in one study
  15. 2019 High

    Revealed a non-apoptotic stabilizing role for DLC binding, with DYNLL-induced oligomerization protecting BMF from ubiquitin-independent 20S proteasomal degradation and modulating Bim.

    Evidence Co-IP, cell-free reconstitution, 20S degradation assays and DYNLL-binding-deficient mutants

    PMID:31189926

    Open questions at the time
    • In vivo significance of BMF-driven Bim degradation not established
  16. 2021 High

    Provided the structural and kinase basis for BMF release, with p38 phosphorylating Thr72—a direct DLC2-contacting residue—to sterically disrupt the interaction.

    Evidence In vitro kinase assay, X-ray crystallography of the BMF/DLC2 complex and phosphomimetic knock-in mice; plus FOXM1 cis-regulatory control of BMF

    PMID:34035233 PMID:34462553

    Open questions at the time
    • Coordination of p38, JNK and ERK phosphorylation events not temporally resolved
  17. 2023 High

    Defined the partner-selectivity determinants of the BMF BH3 helix, explaining high affinity for Bcl-2/Bcl-xL and weak Mcl-1 binding.

    Evidence Fluorescence polarization binding and crystal structures of BMF BH3 bound to Bcl-2, Bcl-xL and Mcl-1 with mutagenesis

    PMID:37560128

    Open questions at the time
    • Functional consequence of selective Mcl-1 sparing in cells not directly tested here
  18. 2026 Medium

    Extended chromatin repression of BMF to cancer therapy, showing DNTTIP1/MiDAC and RBMS2 control BMF in leukemia and breast cancer chemoresponse.

    Evidence ChIP-qPCR/CUT&Tag with DNTTIP1 knockdown in leukemia models; RIP and functional rescue for RBMS2 mRNA stabilization

    PMID:35280673 PMID:41603084

    Open questions at the time
    • Single-lab studies
    • Direct binding sites of RBMS2 on BMF mRNA not mapped at nucleotide resolution

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many transcriptional, translational, phospho-, and stability inputs are quantitatively integrated to set the apoptotic threshold in a given cell, and whether BMF ever directly activates Bax/Bak in mammalian cells, remain unresolved.
  • No unified model coupling input strength to BMF release and killing
  • Direct vs indirect Bax/Bak activation in mammals untested
  • In vivo contribution of isoform/stability control unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140313 molecular sequestering activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 2
Partners
BCL2BCL2L1BCL2L11DYNLL1DYNLL2MCL1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 BMF is a BH3-only protein that is sequestered to myosin V motors via association with dynein light chain 2 (DLC2) in healthy cells. Upon loss of cell attachment (anoikis), BMF is released from this cytoskeletal anchor, translocates, and binds prosurvival Bcl-2 proteins to trigger apoptosis. The BH3 domain is required both for binding prosurvival Bcl-2 proteins and for inducing apoptosis. Co-immunoprecipitation, subcellular fractionation, domain mutagenesis, overexpression apoptosis assay Science High 11546872
2006 BMF, Bim, and Bad are intrinsically unstructured proteins (IUPs) in the absence of binding partners. Upon binding to prosurvival Bcl-2 proteins, only the BH3 element of BMF/Bim becomes structured (coupled folding and binding), while most residues remain disordered. NMR spectroscopy, circular dichroism, sequence analysis Cell Death and Differentiation High 16645638
2007 BMF mRNA is transcriptionally upregulated upon loss of matrix attachment or disruption of the actin cytoskeleton (but not other stresses) during anoikis and mammary acinar morphogenesis. Constitutive activation of MEK/ERK or PI3K/AKT pathways suppresses this transcriptional upregulation. BMF knockdown is sufficient to prevent anoikis and luminal apoptosis. Microarray, siRNA knockdown, 3D mammary acinar culture, anchorage-independent growth assay PNAS High 17360431
2006 TGF-β induces apoptosis by transcriptionally upregulating BMF and Bim in a manner dependent on Smad4, p38 MAPK, and reactive oxygen species. TGF-β-induced BMF localizes to cellular membranes implicated in apoptosis. Simultaneous inhibition of both BMF and Bim expression provides significant protection from TGF-β-induced apoptosis. siRNA knockdown, gene expression analysis, Smad4 knockout cells, pathway inhibitors, subcellular fractionation Oncogene Medium 16909112
2006 HDAC inhibitors FK228 and CBHA induce BMF transcription by causing histone H3 and H4 hyperacetylation specifically at the BMF promoter region. BMF knockdown rescues cells from HDAC inhibitor-induced apoptosis, disruption of mitochondrial membrane potential, and DNA fragmentation, establishing BMF as a central mediator of HDAC inhibitor-induced apoptosis. Chromatin immunoprecipitation (ChIP), siRNA knockdown, Western blot, HDAC1 overexpression, cell viability assay Cell Death and Differentiation High 15947789
2008 Bmf-deficient mice develop B cell-restricted lymphadenopathy due to abnormal resistance of B cells to apoptotic stimuli. Loss of Bmf specifically protects lymphocytes against glucocorticoid- or HDAC inhibitor-induced apoptosis, but not anoikis or UV irradiation. Bmf deficiency accelerates γ-irradiation-induced thymic lymphoma, identifying Bmf as a tumor suppressor. Bmf knockout mouse generation, in vivo lymphocyte homeostasis analysis, ex vivo apoptosis assays with defined stimuli Journal of Experimental Medicine High 18299399
2009 MEK inhibition induces BMF translocation from cytoskeleton to cytosol in apoptosis-sensitive melanoma cells, but in resistant cells BMF remains sequestered via DLC2 binding. A BMF mutant (A69P) with decreased DLC2 binding promotes apoptosis in resistant cells, while a BH3 domain mutation (L138A) abolishes this effect, demonstrating that both DLC2 dissociation and BH3-mediated interactions are required for BMF apoptotic activity. Subcellular fractionation, immunofluorescence, BMF mutant overexpression (A69P, L138A), siRNA knockdown, MEK inhibitor treatment Cancer Research High 19244105
2010 JNK is required for BMF (and Bim) release from the cytoskeleton fraction upon Neisseria gonorrhoeae infection, and this release depends on upstream Rac-1 activation. Depletion of Bim and Bmf synergistically prevents Bak/Bax activation and caspase activation. Apoptosis in Bmf-depleted cells can be reconstituted by silencing antiapoptotic Bcl-XL. Focused siRNA screen, cytoskeletal fractionation, JNK inhibition, Rac-1 depletion, caspase activation assay PLoS Pathogens Medium 19300516
2010 In breast cancer cells, paclitaxel induces a displacement mechanism where BMF (and Puma) competitively displace Bim from antiapoptotic proteins, leading to Bax/Bak activation. Both Bim and BMF are required for paclitaxel toxicity; an increase in Bim levels is not required. Co-immunoprecipitation, siRNA knockdown of individual BH3-only proteins, BH3 profiling Cell Death and Differentiation Medium 20431602
2010 Bmf is generated as two isoforms (Bmf-CUG and Bmf-short) from a common transcript via CUG-initiated translation. Both isoforms localize preferentially to the outer mitochondrial membrane, display comparable binding affinities to prosurvival Bcl-2 family members, and induce rapid Bcl-2-blockable apoptosis. Endogenous Bmf expression is induced by stresses that repress CAP-dependent translation (serum deprivation, hypoxia, PI3K/AKT or mTOR inhibition, eIF-4E inhibition). Gene locus characterization, CUG mutagenesis, subcellular fractionation, co-immunoprecipitation, siRNA knockdown, apoptosis assay Cell Death and Differentiation Medium 20706276
2010 Bmf Ser74 phosphorylation by JNK contributes to a moderate increase in Bmf apoptotic activity. Bmf and Bim have partially redundant functions in vivo: developmental ablation of interdigital webbing and normal lymphocyte homeostasis require cooperative activity of both proteins. Loss of Bmf alone causes uterovaginal developmental defects (imperforate vagina, hydrometrocolpos). Bmf knock-in mice with phosphorylation-site mutations (Ser74 → Ala and Ser74 → Glu), compound Bim/Bmf knockout mice, in vivo developmental phenotyping Molecular and Cellular Biology High 19841067
2010 Hypoxia suppresses expression of BMF (and Bim) in mammary epithelial cells, protecting them from anoikis and blocking luminal clearing during acinar morphogenesis. This protection is associated with increased EGFR-MEK-ERK activation and requires the hypoxia-activated transcription factor HIF. 3D mammary acinar culture, siRNA knockdown, hypoxia chamber, ERK inhibition, Western blot Molecular Biology of the Cell Medium 20861305
2011 BMF is a central regulator of anoikis in human intestinal epithelial cells (IECs). Upon loss of cell attachment, BMF localizes to mitochondria. RNAi-mediated knockdown of BMF reduces apoptosis and caspase-3 activity, and leads to increased phospho-AKT, supporting BMF's role in conveying cytoskeletal damage signals to the mitochondrial apoptosis pathway. Bmf-deficient mice (DSS colitis model), primary human IEC fractionation, Western blot, siRNA knockdown, caspase-3 activity assay Journal of Biological Chemistry High 21673109
2012 ERK2 directly phosphorylates BMF on serine 74 and serine 77, with Ser77 being the predominant site. Ser77 phosphorylation reduces BMF pro-apoptotic activity through a mechanism independent of altering BMF localization to mitochondria or its interactions with DLC2 or prosurvival proteins (Bcl-XL, Bcl-2, Mcl-1). In vitro kinase assay with ERK2, phospho-specific antibodies, BMF Ser77 point mutants, mitochondrial fractionation, Co-immunoprecipitation Cell Death & Disease High 22258404
2013 IFN-γ downregulates BMF expression in a p53-dependent manner. IFN-γ increases nuclear p53 levels and promotes p53 interaction with the BMF promoter. IFN-γ-induced p53-HDAC1 interaction leads to deacetylation of p53, which suppresses BMF expression. Suppression of BMF by deacetylated p53 facilitates IFN-γ-induced autophagy by reducing Beclin-1/Bcl-2 interaction. bmf-/- cells show prominent autophagy. ChIP, Co-immunoprecipitation (p53-HDAC1), p53 mutant analysis, bmf knockout cells, autophagy assay (Beclin-1/Bcl-2 interaction) Journal of Cell Biology High 23629966
2014 HDAC8 directly represses the BMF gene. On the BMF promoter, loss of HDAC8 is associated with STAT3/Sp3 transcription factor exchange and recruitment of p300. STAT3 represses BMF transcription, while p300 promotes it. Overexpression of HDAC8 interferes with BMF induction; STAT3 silencing activates BMF. ChIP, siRNA knockdown of HDAC8 and STAT3, p300 inhibitor treatment, HDAC8 overexpression, promoter analysis Cell Death & Disease High 25321483
2010 AMPK activation (in response to bioenergetic stress from HNF1A inactivation) mediates transcriptional induction of BMF, coupling energy stress to apoptosis. AMPK activation is sufficient to induce apoptosis in naive cells; BMF siRNA knockdown protects against HNF1A-inactivation-induced apoptosis. siRNA knockdown of AMPKα and BMF, pharmacological AMPK activation (AICAR) and inhibition (Compound C), gene expression analysis, flow cytometry Journal of Biological Chemistry Medium 20841353
2004 Two novel human BMF isoforms (Bmf-II and Bmf-III) that lack the BH3 domain but retain the DLC2-binding domain were identified in B-CLL cells. Bmf-I (the original isoform) induces apoptosis and reduces colony formation; Bmf-II and Bmf-III have no apoptotic activity and instead increase colony formation. BMF expression is regulated by transcriptional activation and alternative splicing. cDNA cloning, overexpression in HeLa cells, colony formation assay, apoptosis assay, Northern blot Leukemia Medium 14574334
2016 FOXO3 is a direct transcriptional activator of BMF. E-cadherin inactivation in breast cancer cells induces PI3K/AKT-dependent FOXO3 inhibition, which suppresses BMF upregulation upon anchorage loss, leading to anoikis resistance. Re-expression of BMF in E-cadherin-negative metastatic breast cancer cells is sufficient to inhibit tumor growth and dissemination in mice. ChIP (FOXO3 binding to BMF promoter), PI3K/AKT inhibition, BMF overexpression in xenograft model, siRNA knockdown Cell Death and Differentiation High 27035620
2021 p38 MAPK directly phosphorylates BMF at multiple sites including a non-proline-directed site threonine 72 (T72). Crystallographic studies show that T72 directly participates in DLC2 binding; T72 phosphorylation blocks the BMF/DLC2 interaction through steric hindrance, triggering BMF release from the cytoskeleton. Phosphomimetic mutation of T72 enhances BMF apoptotic activity in vitro and in a knock-in mouse model. In vitro kinase assay, X-ray crystallography (BMF/DLC2 complex structure), phosphomimetic knock-in mouse, anoikis assay, p38 inhibition Cell Death and Differentiation High 34462553
2019 DYNLL1 and DYNLL2 (dynein light chain isoforms) both interact with BMF and induce its homo-dimerization and formation of ternary Bim-DYNLL-Bmf complexes in cell-free and cellular systems. DYNLL-induced oligomerization stabilizes BMF by inhibiting its degradation by the ubiquitin-independent 20S proteasome. Wild-type BMF (but not DYNLL-binding-deficient mutant) overexpression induces degradation of endogenous Bim, modulating Bim-DYNLL association. Co-immunoprecipitation, cell-free reconstitution system, 20S proteasome degradation assay, DYNLL-binding-deficient BMF mutant, Western blot in multiple cell lines Cell Death and Differentiation High 31189926
2023 The BMF BH3 peptide binds with high affinity to prosurvival Bcl-2 and Bcl-xL, but with much lower affinity to Mcl-1. Crystal structures of the BMF BH3 peptide in complex with Bcl-2, Bcl-xL, and Mcl-1 show that the α-helical BMF BH3 occupies the canonical groove with conserved hydrophobic and salt bridge interactions for Bcl-2/Bcl-xL, but the conserved Asp-Arg salt bridge is absent in the Mcl-1/BMF BH3 complex. Mutational analysis confirmed residue-specific affinity determinants. Binding assays (fluorescence polarization), X-ray crystallography of three BMF BH3 complexes, site-directed mutagenesis Computational and Structural Biotechnology Journal High 37560128
2013 In yeast reconstitution experiments, BMF (Noxa, Bik, tBid) can only promote cell death when both multidomain proapoptotic (Bax/Bak) AND antiapoptotic Bcl-2 family proteins are present. BMF cannot induce cell death in the absence of antiapoptotic proteins in this system, suggesting BMF activates Bax/Bak indirectly by inhibiting antiapoptotic proteins (indirect activation model). Yeast cell death reconstitution assay with defined combinations of Bcl-2 family members FEMS Yeast Research Medium 23991648
2009 Bmf suppresses c-Myc-driven B-cell lymphomagenesis by mediating apoptosis in immature IgM+ B cells. c-Myc represses Bmf expression in premalignant pre-B cells. Loss of Bmf reduces selective pressure to inactivate p53, identifying Bmf as a component of a p53-independent tumor suppressor pathway triggered by c-Myc. Eμ-myc/bmf-/- compound mutant mice, flow cytometry of tumor immunophenotypes, apoptosis assays, p53 status analysis Blood High 19965635
2016 A SNP (rs539846 C>A) in a super-enhancer within intron 3 of BMF alters a conserved RELA-binding motif, disrupts RELA binding, and is associated with decreased BMF expression in CLL, linking reduced BMF-mediated apoptosis to CLL susceptibility. Chromatin accessibility mapping, ChIP for RELA binding, luciferase reporter assay, CRISPR/allele-specific expression analysis, histone H3K27ac ChIP-seq Cell Reports Medium 27524613
2021 FOXM1 binds to a BMF intronic cis-regulatory element that interacts with both the BMF and the neighbor gene BUB1B promoter regions, oppositely regulating their expression. FOXM1 repression leads to BMF upregulation, which increases death in mitosis (DiM) upon antimitotic drug treatment. ChIP, 3C/chromatin conformation, siRNA knockdown, BMF knockdown, antimitotic drug treatment, live-cell imaging Cell Death & Disease Medium 34035233
2015 Mutant p53-R273H (but not p53-R175H) suppresses BMF expression through constitutively active PI3K/AKT signaling, conferring anoikis resistance. Silencing p53-R273H reduces AKT phosphorylation and induces BMF expression. PI3K/AKT blockade reverses BMF suppression. siRNA knockdown of endogenous p53-R273H, AKT phosphorylation analysis, suspension culture anoikis assay, PI3K inhibition Cell Death & Disease Medium 26181206
2022 RBMS2 (RNA binding motif single-stranded interacting protein 2) positively regulates BMF expression at the post-transcriptional level. RIP assay demonstrated RBMS2 binding to BMF mRNA. RBMS2-mediated BMF upregulation increases caspase-3, caspase-9, and PARP cleavage and sensitizes breast cancer cells to doxorubicin. The chemosensitizing effect of RBMS2 is reversed by BMF inhibition. RIP (RNA immunoprecipitation) assay, dual-luciferase reporter assay, flow cytometry, xenograft model International Journal of Biological Sciences Medium 35280673
2017 BMF is required for the hormonally-driven depletion of the primordial follicle reserve during puberty in mice. BMF-deficient females retain significantly more primordial follicles after puberty, demonstrating BMF is essential for this developmental apoptotic process via the intrinsic pathway. BMF knockout mouse analysis, follicle counting, hormonal manipulation (gonadotropin treatment) Cell Death & Disease Medium 28771225
2026 DNTTIP1, within the MiDAC complex, recruits HDAC1/2 to the BMF promoter to silence BMF expression via histone H3K27 deacetylation in acute leukemia. DNTTIP1 depletion leads to H3K27 hyperacetylation at the BMF promoter, reactivates BMF, disrupts BCL2-mediated survival, and triggers autophagy and apoptosis. RNA-seq, CUT&Tag (H3K27ac), ATAC-seq, ChIP-qPCR at BMF promoter, DNTTIP1 knockdown, in vivo leukemia mouse models Clinical and Translational Medicine Medium 41603084
2025 In multiple myeloma (MM), STAT1 transcriptionally regulates Kaiso expression, and Kaiso recruits HDAC1 to the BMF promoter to maintain its repressive state. Depletion of Kaiso or HDAC1 elevates BMF levels and induces MM cell apoptosis. Exogenous Kaiso expression rescues STAT1-depleted MM cells from apoptosis by reversing elevated BMF levels. siRNA knockdown of STAT1/Kaiso/HDAC1, ChIP (Kaiso/HDAC1 at BMF promoter), Kaiso overexpression rescue, apoptosis assay bioRxiv (preprint)preprint Low bio_10.1101_2025.09.29.675399

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science (New York, N.Y.) 501 11546872
2009 MicroRNA-221 targets Bmf in hepatocellular carcinoma and correlates with tumor multifocality. Clinical cancer research : an official journal of the American Association for Cancer Research 265 19671867
2006 Bim, Bad and Bmf: intrinsically unstructured BH3-only proteins that undergo a localized conformational change upon binding to prosurvival Bcl-2 targets. Cell death and differentiation 182 16645638
2009 MiR-125b expression affects the proliferation and apoptosis of human glioma cells by targeting Bmf. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 139 19471102
2007 Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and morphogenesis. Proceedings of the National Academy of Sciences of the United States of America 123 17360431
2006 Upregulation of two BH3-only proteins, Bmf and Bim, during TGF beta-induced apoptosis. Oncogene 117 16909112
2008 Loss of the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development. The Journal of experimental medicine 109 18299399
2008 Bim and Bmf in tissue homeostasis and malignant disease. Oncogene 105 19641506
2006 Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA-induced apoptosis. Cell death and differentiation 99 15947789
2015 Mutant p53-R273H mediates cancer cell survival and anoikis resistance through AKT-dependent suppression of BCL2-modifying factor (BMF). Cell death & disease 90 26181206
2021 Exosomal microRNA-22-3p alleviates cerebral ischemic injury by modulating KDM6B/BMP2/BMF axis. Stem cell research & therapy 87 33546766
1984 B cell maturation factor (BMF): a lymphokine or family of lymphokines promoting the maturation of B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 83 6606666
2010 Displacement of Bim by Bmf and Puma rather than increase in Bim level mediates paclitaxel-induced apoptosis in breast cancer cells. Cell death and differentiation 71 20431602
2014 HDAC8 and STAT3 repress BMF gene activity in colon cancer cells. Cell death & disease 69 25321483
2008 BH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide-induced cell death in myeloma. Blood 65 18354037
2009 Mitogen-activated protein kinase inhibition induces translocation of Bmf to promote apoptosis in melanoma. Cancer research 61 19244105
2019 lncRNA-ES3/miR-34c-5p/BMF axis is involved in regulating high-glucose-induced calcification/senescence of VSMCs. Aging 58 30654331
2010 Functional cooperation of the proapoptotic Bcl2 family proteins Bmf and Bim in vivo. Molecular and cellular biology 57 19841067
2016 Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism. Cell reports 55 27524613
2010 Hypoxia suppression of Bim and Bmf blocks anoikis and luminal clearing during mammary morphogenesis. Molecular biology of the cell 55 20861305
2009 Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad. Blood 54 19965635
2016 Early generated B1 B cells with restricted BCRs become chronic lymphocytic leukemia with continued c-Myc and low Bmf expression. The Journal of experimental medicine 49 27899442
2019 Upregulation of miR-874-3p decreases cerebral ischemia/reperfusion injury by directly targeting BMF and BCL2L13. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 48 31200256
2016 Restraining FOXO3-dependent transcriptional BMF activation underpins tumour growth and metastasis of E-cadherin-negative breast cancer. Cell death and differentiation 47 27035620
2014 Deregulated cell death and lymphocyte homeostasis cause premature lethality in mice lacking the BH3-only proteins Bim and Bmf. Blood 46 24632712
2011 BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells. The Journal of biological chemistry 44 21673109
2010 BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis. Cell death and differentiation 43 20706276
2013 Deacetylation of p53 induces autophagy by suppressing Bmf expression. The Journal of cell biology 39 23629966
2010 AMP-activated protein kinase mediates apoptosis in response to bioenergetic stress through activation of the pro-apoptotic Bcl-2 homology domain-3-only protein BMF. The Journal of biological chemistry 38 20841353
2004 Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells. Leukemia 36 14574334
2018 miR-221 regulates proliferation and apoptosis of ovarian cancer cells by targeting BMF. Oncology letters 32 30405811
2012 Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf. EMBO molecular medicine 31 23180554
2017 The ovarian reserve is depleted during puberty in a hormonally driven process dependent on the pro-apoptotic protein BMF. Cell death & disease 30 28771225
2009 Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection. PLoS pathogens 30 19300516
2021 Non-canonical phosphorylation of Bmf by p38 MAPK promotes its apoptotic activity in anoikis. Cell death and differentiation 29 34462553
2019 Dynein light chain binding determines complex formation and posttranslational stability of the Bcl-2 family members Bmf and Bim. Cell death and differentiation 25 31189926
2013 Bmf upregulation through the AMP-activated protein kinase pathway may protect the brain from seizure-induced cell death. Cell death & disease 25 23618904
2008 Phosphorylation of mitogen-activated protein kinase 8 (MAPK8) is associated with germ cell apoptosis and redistribution of the Bcl2-modifying factor (BMF). Journal of andrology 25 18222916
2006 Bmf contributes to histone deacetylase inhibitor-mediated enhancing effects on apoptosis after ionizing radiation. Apoptosis : an international journal on programmed cell death 25 16830229
2017 Displacement of Bax by BMF Mediates STARD13 3'UTR-Induced Breast Cancer Cells Apoptosis in an miRNA-Depedent Manner. Molecular pharmaceutics 24 29179557
2012 ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity. Cell death & disease 23 22258404
2018 The pro-apoptotic protein Bmf co-operates with Bim and Puma in neuron death induced by β-amyloid or NGF deprivation. Molecular and cellular neurosciences 21 29499358
2016 Reciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer. Cancer letters 21 27539959
2014 FGFR4 signaling couples to Bim and not Bmf to discriminate subsets of alveolar rhabdomyosarcoma cells. International journal of cancer 20 24550147
2022 RBMS2 Chemosensitizes Breast Cancer Cells to Doxorubicin by Regulating BMF Expression. International journal of biological sciences 19 35280673
2021 Downregulation of lncRNA SNHG14 alleviates neurons injury by modulating the miR-181c-5p/BMF axis in ischemic stroke. Brain research bulletin 18 34224818
2021 FOXM1 repression increases mitotic death upon antimitotic chemotherapy through BMF upregulation. Cell death & disease 17 34035233
2018 MicroRNA-125b inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by targeting BMF. Oncology reports 17 29749531
2015 Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice. Cell death and differentiation 16 25698446
2013 BH3-only proteins Noxa, Bik, Bmf, and Bid activate Bax and Bak indirectly when studied in yeast model. FEMS yeast research 15 23991648
2012 Minor cell-death defects but reduced tumor latency in mice lacking the BH3-only proteins Bad and Bmf. Oncogene 15 22430207
1995 5-Bromomethyl fluorescein (5-BMF) for derivatization of carboxyl containing analytes for use with laser-induced fluorescence detection. Pharmaceutical research 14 7667203
2022 Smad4 mediates Bmf involvement in sheep granulosa cell apoptosis. Gene 13 35063577
2014 Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury. Cell death & disease 13 25299781
2023 CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis. Translational oncology 10 37499410
2009 Bmf is upregulated by PS-341-mediated cell death of glioma cells through JNK phosphorylation. Molecular biology reports 10 19267218
2022 Alternative Transplantation With Post-Transplantation Cyclophosphamide in Aplastic Anemia: A Retrospective Report From the BMF-WG of Hunan Province, China. Transplantation and cellular therapy 9 36272527
2024 Matrix stiffening facilitates stemness of liver cancer stem cells by YAP activation and BMF inhibition. Biomaterials advances 8 38959652
2023 BMF-AS1/BMF Promotes Diabetic Vascular Calcification and Aging both In Vitro and In Vivo. Aging and disease 8 36818559
2023 Structural basis of the specificity and interaction mechanism of Bmf binding to pro-survival Bcl-2 family proteins. Computational and structural biotechnology journal 8 37560128
2023 Transforming growth factor-β1 mediates the SMAD4/BMF pathway to regulate ovarian granulosa cell apoptosis in small tail Han sheep. Theriogenology 8 37979327
2022 Upregulation of miR-29b-3p alleviates coronary microembolization-induced myocardial injury via regulating BMF and GSK-3β. Apoptosis : an international journal on programmed cell death 7 36315357
2025 Bcl-2 modifying factor (Bmf): "a mysterious stranger" in the Bcl-2 family proteins. Cell death and differentiation 6 40849581
2015 BH3-Only protein bmf is required for the maintenance of glucose homeostasis in an in vivo model of HNF1α-MODY diabetes. Cell death discovery 6 27551471
2021 [Aldehyde degradation deficiency (ADD) syndrome: discovery of a novel fanconi anemia-like inherited BMF syndrome due to combined ADH5/ALDH2 deficiency]. [Rinsho ketsueki] The Japanese journal of clinical hematology 5 34219079
2024 Emerging genetic technologies informing personalized medicine in Shwachman-Diamond syndrome and other inherited BMF disorders. Blood 4 38905596
2024 Pressure loading regulates the stemness of liver cancer stem cells via YAP/BMF signaling axis. Journal of cellular physiology 4 39358905
2022 MiR-125b-5p ameliorates hypoxia/reoxygenation-induced endothelial cell dysfunction and attenuates reduced uterine perfusion pressure-induced hypertension in pregnant rats via targeting BMF. Hypertension in pregnancy 4 35171055
2007 Mutational analysis of the BH3 domains of proapoptotic Bcl-2 family genes Bad, Bmf and Bcl-G in laryngeal squamous cell carcinomas. Tumori 4 17557568
2006 BH3 domain mutation of proapoptotic genes Bad, Bmf and Bcl-G is rare in transitional cell carcinomas of the urinary bladder. Pathology 4 16484005
2022 Circ_0001360 absence alleviates oxygen-glucose deprivation/reoxygenation-induced SK-N-SH cell injury via controlling the miR-671-5p/BMF pathway. The International journal of neuroscience 3 36039693
2007 Characterization of the BH3 protein Bmf in Gallus gallus: identification of a novel chicken-specific isoform. Gene 3 17967519
2003 Evolutionary learning of BMF fuzzy-neural networks using a reduced-form genetic algorithm. IEEE transactions on systems, man, and cybernetics. Part B, Cybernetics : a publication of the IEEE Systems, Man, and Cybernetics Society 3 18238247
2023 LncRNA RP11-521C20.3 Inhibits Cigarette Smoke Extract-Induced Apoptosis in A549 Cells by Targeting BMF Signaling. International journal of chronic obstructive pulmonary disease 1 37114104
2026 DNTTIP1 drives leukaemogenesis through MiDAC-mediated epigenetic silencing of BMF. Clinical and translational medicine 0 41603084
2025 SNAI2 cooperates with MEK1/2 and HDACs to suppress BIM- and BMF-dependent apoptosis in TERT promoter mutant cancers. PloS one 0 40560846
2024 VAV1 regulates cell growth in cutaneous T-cell lymphoma via the BAMBI/BMF signalling pathway. European journal of dermatology : EJD 0 39589030
2023 An acquired BMF with FANCL gene heterozygous mutation: Case report. Medicine 0 37327301

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