Affinage

BMF

Bcl-2-modifying factor · UniProt Q96LC9

Length
184 aa
Mass
20.5 kDa
Annotated
2026-04-28
78 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMF is a BH3-only proapoptotic member of the Bcl-2 family that functions as a sentinel linking cytoskeletal integrity and diverse stress signals to mitochondrial apoptosis. In healthy cells, BMF is sequestered to the actin cytoskeleton via dynein light chain (DYNLL1/DYNLL2) binding to myosin V motors; upon loss of cell attachment (anoikis), infection, or drug treatment, stress-activated kinases such as p38 MAPK (phosphorylating T72 to sterically disrupt DLC2 binding) and JNK release BMF, which translocates to mitochondria where its intrinsically disordered BH3 domain undergoes coupled folding and binding to neutralize prosurvival Bcl-2, Bcl-xL, and (with lower affinity) Mcl-1, thereby enabling Bax/Bak-dependent apoptosis (PMID:11546872, PMID:34462553, PMID:37560128, PMID:16645638). BMF transcription is positively regulated by FOXO3, RELA-dependent super-enhancer activity, TGF-β/Smad4 signaling, and histone hyperacetylation (opposed by HDAC8/STAT3 and the DNTTIP1/MiDAC complex), while being suppressed by PI3K/AKT, ERK2 phosphorylation of Ser77, and oncogenic p53 mutants; DYNLL-induced oligomerization further stabilizes BMF protein by protecting it from ubiquitin-independent 20S proteasomal degradation (PMID:27035620, PMID:25321483, PMID:41603084, PMID:22258404, PMID:31189926). Bmf-deficient mice develop B-cell lymphadenopathy and are resistant to glucocorticoid- and HDAC-inhibitor-induced lymphocyte apoptosis, establishing BMF as a tumor suppressor, and a CLL-risk SNP (rs539846) in a BMF intronic super-enhancer impairs RELA binding and reduces BMF expression, linking BMF regulation to chronic lymphocytic leukemia susceptibility (PMID:18299399, PMID:27524613).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    The foundational question of BMF's identity and mechanism was answered: BMF was identified as a new BH3-only protein sequestered to myosin V motors via DLC2, released upon anoikis to bind prosurvival Bcl-2 proteins and trigger apoptosis — establishing the cytoskeletal-sequestration model of apoptotic regulation.

    Evidence Co-immunoprecipitation, domain mutagenesis, subcellular fractionation, and apoptosis assays in mammalian cells

    PMID:11546872

    Open questions at the time
    • No structural detail on how BMF engages DLC2 or prosurvival proteins
    • Upstream signals triggering BMF release from cytoskeleton not defined
    • In vivo genetic validation absent
  2. 2004 Medium

    Alternative splicing of BMF was shown to generate isoforms (Bmf-II, Bmf-III) lacking the BH3 domain that cannot induce apoptosis, demonstrating the BH3 domain is the obligate effector element and suggesting splice regulation could modulate BMF function.

    Evidence cDNA cloning, expression in HeLa cells, colony formation and apoptosis assays

    PMID:14574334

    Open questions at the time
    • Physiological expression levels and tissue distribution of non-BH3 isoforms unclear
    • Whether BH3-lacking isoforms act as dominant-negatives not directly tested
  3. 2006 High

    Two key properties of BMF were established: (1) BMF is intrinsically disordered, with only the BH3 element undergoing coupled folding and binding upon engagement with prosurvival Bcl-2 proteins, and (2) BMF transcription is induced by TGF-β via Smad4/p38 and by HDAC inhibitors via promoter hyperacetylation, placing BMF downstream of both cytokine and epigenetic stress pathways.

    Evidence NMR/CD spectroscopy (structural); siRNA, ChIP, subcellular fractionation, and apoptosis assays (transcriptional)

    PMID:15947789 PMID:16645638 PMID:16909112

    Open questions at the time
    • Structure of full-length BMF in complex with DLC2 unknown
    • Relative contribution of Bmf versus Bim in TGF-β apoptosis not quantified
  4. 2007 High

    BMF was established as a transcriptional target upregulated during anoikis and mammary morphogenesis, with MEK/ERK and PI3K/AKT pathways actively suppressing its expression — explaining how oncogenic signaling silences this apoptotic checkpoint to enable anchorage-independent growth.

    Evidence siRNA knockdown, microarray, 3D acinar culture, anchorage-independent growth assay in mammary epithelial cells

    PMID:17360431

    Open questions at the time
    • Transcription factors mediating ERK/AKT-dependent repression not identified
    • Relative importance of transcriptional versus post-translational regulation during anoikis unclear
  5. 2008 High

    In vivo genetic evidence established BMF as a bona fide tumor suppressor: Bmf-knockout mice showed impaired glucocorticoid- and HDAC-inhibitor-induced lymphocyte apoptosis, B-cell lymphadenopathy, and accelerated thymic lymphomagenesis, resolving whether BMF's proapoptotic function is physiologically relevant.

    Evidence Bmf knockout mouse, flow cytometry, apoptosis assays, tumor incidence analysis

    PMID:18299399

    Open questions at the time
    • Whether Bmf loss cooperates with specific oncogenes beyond irradiation not tested
    • Tissue specificity of tumor suppression beyond lymphoid cells unknown
  6. 2009 High

    The cytoskeletal release model was mechanistically validated: MEK inhibition in melanoma triggered BMF translocation from cytoskeleton to cytosol, and a DLC2-binding-deficient mutant (A69P) was sufficient to drive apoptosis in resistant cells, while BH3 mutation (L138A) abolished it; separately, Bim and Bmf were shown to cooperate synergistically in infection-triggered apoptosis via JNK/Rac1-dependent cytoskeletal release.

    Evidence Subcellular fractionation, mutagenesis, overexpression, siRNA in melanoma; siRNA screen and epistasis in Neisseria infection model

    PMID:19244105 PMID:19300516

    Open questions at the time
    • Kinase directly phosphorylating BMF for cytoskeletal release not identified in these studies
    • Relative contributions of Bim versus Bmf in different cell types not resolved
  7. 2010 High

    Multiple regulatory layers were mapped: JNK phosphorylates Bmf at Ser74 to modulate proapoptotic activity in vivo (knock-in mice), Bim and Bmf cooperate in developmental apoptosis; CUG-initiated translation produces a longer Bmf isoform (Bmf-CUG) with comparable function; and AMPK activates Bmf transcription under bioenergetic stress.

    Evidence Knock-in phosphomutant mice, compound mutant developmental analysis, molecular cloning with KO validation, pharmacological AMPK epistasis

    PMID:19841067 PMID:20706276 PMID:20841353

    Open questions at the time
    • Which kinase(s) target T72 versus S74 not distinguished
    • Physiological ratio of Bmf-CUG to Bmf-short and functional differences unclear
  8. 2012 High

    ERK2 was identified as a direct kinase phosphorylating BMF at Ser77 (predominant site) to suppress its proapoptotic activity — surprisingly through a mechanism independent of altering mitochondrial localization or DLC2/Bcl-2 protein interactions, revealing a distinct inhibitory phosphorylation from the JNK-Ser74 activating event.

    Evidence In vitro kinase assay, site-directed mutagenesis, subcellular fractionation, co-immunoprecipitation, apoptosis assays

    PMID:22258404

    Open questions at the time
    • Mechanism by which Ser77 phosphorylation inhibits BMF without changing known interactions undefined
    • Whether ERK2-Ser77 and JNK-Ser74 phosphorylation are mutually exclusive or coexist not tested
  9. 2013 High

    Two conceptual advances were made: (1) deacetylated p53 directly represses the BMF promoter, and BMF loss facilitates autophagy by freeing Beclin-1 from Bcl-2, linking BMF to autophagy regulation beyond apoptosis; (2) yeast reconstitution showed BMF activates Bax/Bak indirectly by sequestering antiapoptotic proteins rather than directly activating effectors.

    Evidence ChIP, co-IP, luciferase reporter, bmf KO cells (p53 study); yeast reconstitution with genetic epistasis (indirect activation model)

    PMID:23629966 PMID:23991648

    Open questions at the time
    • Whether BMF-Beclin-1 axis operates in non-immune cells not tested
    • Direct activation model not fully excluded in mammalian cells
  10. 2014 High

    HDAC8 and STAT3 were identified as direct transcriptional repressors of the BMF promoter, with HDAC8 loss causing STAT3/Sp3 exchange and p300 recruitment — providing a molecular mechanism for HDAC-inhibitor-induced BMF activation first observed in 2006.

    Evidence ChIP, siRNA, overexpression, reporter assays, HDAC inhibitor treatment in neuroblastoma cells

    PMID:25321483

    Open questions at the time
    • Whether HDAC8-specific inhibitors are sufficient for BMF induction in vivo not shown
    • Role of other HDACs at the BMF promoter not systematically assessed
  11. 2016 High

    Two transcriptional activation mechanisms were defined: FOXO3 was identified as a direct transcriptional activator of BMF during anoikis (suppressed by PI3K/AKT in E-cadherin-negative tumors), and a CLL-risk SNP (rs539846) in a BMF intronic super-enhancer was shown to disrupt RELA binding, reducing BMF expression and linking BMF regulation to CLL susceptibility.

    Evidence ChIP, reporter assays, siRNA, xenograft model (FOXO3); ATAC-seq, ChIP-seq, RELA binding assays (CLL SNP)

    PMID:27035620 PMID:27524613

    Open questions at the time
    • Whether FOXO3 and RELA act independently or cooperatively on BMF transcription unknown
    • Functional validation of the CLL SNP in isogenic cell lines not performed
  12. 2019 High

    The DLC interaction was recharacterized: both DYNLL1 and DYNLL2 bind BMF and induce homodimerization as well as ternary Bim–DYNLL–Bmf complexes; critically, DYNLL-induced oligomerization stabilizes BMF by protecting it from ubiquitin-independent 20S proteasomal degradation, revealing a protein-stability function for cytoskeletal sequestration beyond simple localization.

    Evidence Co-immunoprecipitation, cell-free proteasome degradation assay, mutagenesis in multiple cell lines

    PMID:31189926

    Open questions at the time
    • Whether DYNLL-BMF oligomers form in vivo at endogenous levels not confirmed
    • How BMF overexpression promotes Bim degradation via DYNLL competition not fully resolved
  13. 2021 High

    Structural resolution of two key BMF interactions was achieved: p38 MAPK phosphorylates BMF at T72, and crystallography showed T72 directly contacts DLC2, with phosphorylation sterically blocking DLC2 binding — providing the first atomic mechanism for stress-induced BMF release; additionally, FOXM1 was shown to repress BMF via an intronic cis-regulatory element.

    Evidence Crystal structure of BMF-DLC2 complex, in vitro kinase assay, knock-in mouse (p38/T72); ChIP, 3C chromatin conformation, siRNA (FOXM1)

    PMID:34035233 PMID:34462553

    Open questions at the time
    • Full-length BMF structure still unavailable
    • Whether p38 and JNK phosphorylation events are sequential or context-specific not resolved
  14. 2023 High

    Crystal structures of BMF BH3 peptide with Bcl-2, Bcl-xL, and Mcl-1 revealed conserved helical binding but absence of a key Asp-Arg salt bridge in the Mcl-1 complex, providing a structural explanation for BMF's lower Mcl-1 affinity and completing the structural basis for BMF's selectivity among prosurvival targets.

    Evidence X-ray crystallography of three complexes, binding affinity assays, site-directed mutagenesis

    PMID:37560128

    Open questions at the time
    • Whether BMF selectivity can be engineered for therapeutic BH3 mimetics not explored
    • Structural basis for BMF interaction with A1/BFL1 not determined
  15. 2026 High

    The DNTTIP1/MiDAC complex was shown to recruit HDAC1/2 to silence the BMF promoter via H3K27 deacetylation; DNTTIP1 loss reactivated BMF, disrupted BCL2-mediated survival, and triggered both autophagy and apoptosis in acute leukemia, identifying a specific chromatin complex responsible for BMF silencing in hematologic malignancy.

    Evidence RNA-seq, CUT&Tag, ATAC-seq, ChIP-qPCR, siRNA knockdown, in vivo leukemia mouse models

    PMID:41603084

    Open questions at the time
    • Whether MiDAC-mediated BMF repression operates in solid tumors not tested
    • Therapeutic window for MiDAC inhibition to reactivate BMF not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of BMF, the mechanistic basis of ERK2-Ser77 phosphorylation inhibiting BMF proapoptotic activity without altering known interactions, context-dependent hierarchy among the multiple transcriptional inputs to the BMF locus, and whether BMF's autophagy-regulatory function through Beclin-1/Bcl-2 modulation is physiologically significant across tissues.
  • Full-length BMF structure not solved
  • Mechanism of Ser77 phosphorylation-mediated inhibition unknown
  • Relative importance of transcriptional versus post-translational BMF regulation in different tissues not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5
Localization
GO:0005856 cytoskeleton 3 GO:0005739 mitochondrion 2 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 6 R-HSA-162582 Signal Transduction 4 R-HSA-9612973 Autophagy 2
Partners
BCL2BCL2L1BIMDYNLL1DYNLL2MCL1

Evidence

Reading pass · 28 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 by association with dynein light chain 2 (DLC2) in healthy cells; loss of cell attachment (anoikis) releases BMF, allowing it to translocate and bind prosurvival Bcl-2 proteins to trigger apoptosis. The BH3 domain is required both for binding prosurvival Bcl-2 proteins and for triggering apoptosis. Co-immunoprecipitation, domain mutagenesis, subcellular fractionation, apoptosis assays Science High 11546872
2006 Bmf (and Bim and Bad) are intrinsically unstructured proteins in the absence of binding partners; upon binding to prosurvival Bcl-2 proteins, only the BH3 element becomes structured (undergoes coupled folding and binding), consistent with a 'bead on a string' molecular recognition mechanism. NMR spectroscopy, CD spectroscopy, sequence analysis Cell death and differentiation High 16645638
2006 TGF-β-induced apoptosis requires Smad4 and p38 MAPK signaling, leading to transcriptional upregulation of both Bmf and Bim; TGF-β-induced Bmf localizes to cellular membranes implicated in apoptosis, and combined inhibition of Bmf and Bim protects cells from TGF-β-induced cell death. siRNA knockdown, gene expression analysis, subcellular fractionation, apoptosis assays Oncogene Medium 16909112
2006 HDAC inhibitors FK228 and CBHA transcriptionally activate Bmf via histone hyperacetylation 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 cell death. ChIP assay, siRNA knockdown, flow cytometry, mitochondrial membrane potential assay Cell death and differentiation High 15947789
2007 Bmf mRNA is transcriptionally upregulated during anoikis and mammary acinar morphogenesis; MEK/ERK or PI3K/AKT pathway activation suppresses this transcriptional upregulation. Bmf knockdown is sufficient to prevent anoikis and luminal apoptosis and promote anchorage-independent growth. siRNA knockdown, microarray, 3D culture morphogenesis assay, anchorage-independent growth assay Proceedings of the National Academy of Sciences High 17360431
2008 Bmf-deficient mice show that Bmf is required for glucocorticoid- and HDAC-inhibitor-induced lymphocyte apoptosis; Bmf protects against B cell lymphadenopathy and accelerates gamma irradiation-induced thymic lymphoma development when absent, demonstrating tumor suppressor function. Knockout mouse, flow cytometry, apoptosis assays, tumor incidence analysis The Journal of experimental medicine High 18299399
2009 MEK inhibition in melanoma induces Bmf translocation from the cytoskeleton (where it is held by DLC2) to cytosol; a Bmf mutant (A69P) with reduced DLC2 binding promotes apoptosis in resistant cells, while BH3 domain mutation (L138A) abolishes this, demonstrating that Bmf release from DLC2 followed by BH3-mediated interactions is required for apoptosis. Subcellular fractionation, mutagenesis, overexpression, siRNA, apoptosis assays Cancer research High 19244105
2009 Bim and Bmf synergistically mediate apoptosis during Neisseria gonorrhoeae infection; both are released from the cytoskeleton fraction upon infection in a JNK-1/Rac-1 dependent manner, and their combined loss prevents Bak/Bax activation and caspase activation. siRNA screen, subcellular fractionation, epistasis (Rac-1/JNK-1), co-immunoprecipitation, caspase assays PLoS pathogens High 19300516
2010 In breast cancer cells treated with paclitaxel, Bmf and Puma competitively displace Bim from antiapoptotic proteins (rather than increasing Bim levels), allowing Bax and Bak activation; both Bim and either Puma or Bmf are required for paclitaxel toxicity. Co-immunoprecipitation, BH3 profiling, siRNA knockdown, flow cytometry Cell death and differentiation Medium 20431602
2010 JNK-mediated phosphorylation of Bmf on Ser74 contributes to increased Bmf activity; knock-in mice with phosphomimetic or non-phosphorylatable Ser74 mutations demonstrate that this phosphorylation modulates Bmf proapoptotic function. Bim and Bmf exhibit partially redundant functions in vivo, cooperating in interdigital webbing ablation and lymphocyte homeostasis. Knock-in mouse generation, compound mutant analysis, developmental phenotyping Molecular and cellular biology High 19841067
2010 AMPK activation in response to bioenergetic stress (induced by dominant-negative HNF1A expression) mediates transcriptional induction of Bmf; Bmf knockdown protects against HNF1A-induced apoptosis, positioning Bmf downstream of AMPK in an energy stress-apoptosis pathway. siRNA knockdown, pharmacological AMPK activation/inhibition, gene silencing, flow cytometry The Journal of biological chemistry Medium 20841353
2010 Bmf gene locus produces two major isoforms (Bmf-CUG and Bmf-short) from a common transcript via CUG-initiated translation; both isoforms bind prosurvival Bcl-2 family members with comparable affinity, localize to the outer mitochondrial membrane, and induce Bcl-2-blockable apoptosis. Endogenous Bmf expression is induced by stress that impairs CAP-dependent translation (serum deprivation, hypoxia, PI3K/AKT/mTOR inhibition). Molecular cloning, subcellular fractionation, co-immunoprecipitation, apoptosis rescue assays, Bmf KO cells Cell death and differentiation High 20706276
2011 BMF localizes to mitochondria during anoikis in intestinal epithelial cells; RNAi-mediated knockdown of BMF reduces caspase-3 activity and apoptosis, and increases phospho-AKT, establishing BMF as a central regulator of anoikis and intestinal epithelial cell homeostasis. Western blot fractionation, RNAi knockdown, caspase-3 assay, Western blot for phospho-AKT, in vivo DSS colitis model The Journal of biological chemistry Medium 21673109
2012 ERK2 directly phosphorylates Bmf on serine 74 and serine 77, with serine 77 being the predominant site; serine 77 phosphorylation reduces Bmf proapoptotic activity through a mechanism independent of altering Bmf localization to mitochondria or interactions with DLC2 or prosurvival Bcl-2 proteins. In vitro kinase assay, site-directed mutagenesis, subcellular fractionation, co-immunoprecipitation, apoptosis assays Cell death & disease High 22258404
2013 Deacetylation of p53 (via IFN-γ-induced HDAC1/p53 interaction) suppresses Bmf expression by increasing p53 binding to the Bmf promoter; suppression of Bmf reduces Beclin-1/Bcl-2 interaction to facilitate autophagy, and bmf-/- cells show prominent autophagy, placing Bmf as a link between p53-mediated transcription and autophagy regulation. ChIP assay, co-immunoprecipitation, luciferase reporter, bmf KO cells, immunoblotting The Journal of cell biology High 23629966
2014 HDAC8 and STAT3 directly repress the BMF gene promoter; loss of HDAC8 leads to STAT3/Sp3 transcription factor exchange and p300 recruitment at the BMF promoter, resulting in BMF induction and apoptosis. HDAC8 overexpression reduces BMF expression and HDAC8 RNAi silencing activates BMF, identifying BMF as a direct target gene of HDAC8 repression. ChIP assay, siRNA knockdown, transient overexpression, reporter assays, HDAC inhibitor treatment Cell death & disease High 25321483
2016 FOXO3 is a direct transcriptional activator of BMF; E-cadherin inactivation in breast cancer cells induces PI3K/AKT-dependent FOXO3 inhibition, preventing BMF upregulation upon loss of anchorage and thereby driving anoikis resistance and tumor dissemination. ChIP assay, reporter assay, siRNA knockdown, anchorage-independence assay, xenograft mouse model Cell death and differentiation High 27035620
2016 A CLL-risk SNP (rs539846 C>A) localizes to a super-enhancer in intron 3 of BMF; the risk allele disrupts a conserved RELA-binding motif, impairs RELA binding to this super-enhancer, and is associated with decreased BMF expression in CLL, mechanistically linking BMF transcriptional regulation to CLL susceptibility. Chromatin accessibility mapping, ChIP-seq, ATAC-seq, reporter assay, RELA binding assay Cell reports Medium 27524613
2019 DYNLL1 and DYNLL2 both interact with Bmf (not just DYNLL2) and induce Bmf homodimerization as well as ternary Bim-DYNLL-Bmf complexes; DYNLL-induced oligomerization stabilizes Bmf by preventing its degradation by the ubiquitin-independent 20S proteasome. Overexpression of wild-type Bmf (but not DYNLL-binding-deficient mutant) induces degradation of endogenous Bim by modulating Bim-DYNLL association. Co-immunoprecipitation, cell-free proteasome degradation assay, mutagenesis, immunoprecipitation in multiple cell lines Cell death and differentiation High 31189926
2021 p38 MAPK directly phosphorylates Bmf at multiple sites including a non-proline-directed site threonine 72 (T72); crystallographic studies reveal that T72 directly participates in DLC2 binding and its phosphorylation blocks Bmf/DLC2 interaction through steric hindrance. Phosphomimetic T72 mutation enhances Bmf apoptotic activity in vitro and in a knock-in mouse model. Crystal structure determination, in vitro kinase assay, mutagenesis, knock-in mouse model, apoptosis assays Cell death and differentiation High 34462553
2021 FOXM1 binds to a BMF intronic cis-regulatory element that interacts with both BMF and BUB1B promoter regions, oppositely regulating their expression; FOXM1 repression leads to BMF upregulation and increased death in mitosis upon antimitotic drug treatment. ChIP assay, 3C/chromatin conformation, siRNA knockdown, reporter assay, cell death assays Cell death & disease Medium 34035233
2023 Crystal structures of the Bmf BH3 peptide in complex with Bcl-2, Bcl-xL, and Mcl-1 reveal that Bmf BH3 adopts an alpha-helical conformation accommodating into the canonical groove; Bmf forms conserved hydrophobic and salt bridge interactions with Bcl-2 and Bcl-xL but the highly conserved Asp-Arg salt bridge is absent in the Mcl-1/Bmf complex, explaining lower Mcl-1 affinity. Mutational analysis validates key residues governing binding specificity. X-ray crystallography, binding affinity assays, site-directed mutagenesis Computational and structural biotechnology journal High 37560128
2004 Two novel isoforms of human Bmf (Bmf-II and Bmf-III) were identified as splice variants lacking the BH3 domain but retaining the DLC2-binding domain; unlike Bmf-I, these isoforms do not induce apoptosis and instead increase colony formation, indicating that the BH3 domain is required for proapoptotic function. cDNA cloning, expression in HeLa cells, colony formation assay, apoptosis assays Leukemia Medium 14574334
2008 In multiple myeloma cells treated with arsenic trioxide, Bmf is upregulated and co-immunoprecipitation demonstrates that Bmf contributes to Bak/Bim release from Bcl-xL; Bmf siRNA silencing significantly protects cells from ATO-induced apoptosis. Co-immunoprecipitation, siRNA knockdown, gene expression profiling, apoptosis assays Blood Medium 18354037
2015 Mutant p53-R273H (contact mutant) suppresses BMF expression through constitutively active PI3K/AKT signaling; silencing p53-R273H reduces AKT phosphorylation and induces BMF expression, sensitizing cells to anoikis. This effect is specific to the R273H contact mutant and not the R175H conformational mutant. siRNA silencing, Western blot, flow cytometry apoptosis assays, suspension culture anoikis assay Cell death & disease Medium 26181206
2013 Using a yeast reconstitution model, BH3-only proteins including Bmf can only promote cell death when both multidomain proapoptotic (Bax/Bak) and antiapoptotic Bcl-2 proteins are present, suggesting Bmf activates Bax/Bak indirectly by binding and inhibiting antiapoptotic proteins (indirect activation model). Yeast reconstitution system, genetic epistasis FEMS yeast research Medium 23991648
2008 MAPK8 (JNK1) phosphorylation correlates with BMF redistribution from cytoskeleton to cytoplasm in testicular germ cells upon loss of Sertoli cell contact; activated p-MAPK8 co-localizes with BMF in round spermatids undergoing apoptosis after detachment. Immunohistochemistry, Western blot, immunocytochemistry in isolated germ cells Journal of andrology Low 18222916
2026 DNTTIP1 within the MiDAC complex recruits HDAC1/2 to silence the BMF promoter (reducing H3K27 acetylation); DNTTIP1 depletion causes H3K27 hyperacetylation at the BMF promoter, reactivating BMF expression, which disrupts BCL2-mediated survival and triggers autophagy and apoptosis in acute leukemia cells. RNA-seq, CUT&Tag, ATAC-seq, ChIP-qPCR, siRNA knockdown, in vivo leukaemia mouse models Clinical and translational medicine High 41603084

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 263 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 104 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 89 26181206
2021 Exosomal microRNA-22-3p alleviates cerebral ischemic injury by modulating KDM6B/BMP2/BMF axis. Stem cell research & therapy 86 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 68 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 60 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 54 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 48 27899442
2019 Upregulation of miR-874-3p decreases cerebral ischemia/reperfusion injury by directly targeting BMF and BCL2L13. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 47 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 31 30405811
2012 Haematopoietic stem cell survival and transplantation efficacy is limited by the BH3-only proteins Bim and Bmf. EMBO molecular medicine 31 23180554
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
2017 The ovarian reserve is depleted during puberty in a hormonally driven process dependent on the pro-apoptotic protein BMF. Cell death & disease 28 28771225
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 16 34035233
2018 MicroRNA-125b inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by targeting BMF. Oncology reports 16 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
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
2022 Smad4 mediates Bmf involvement in sheep granulosa cell apoptosis. Gene 12 35063577
2009 Bmf is upregulated by PS-341-mediated cell death of glioma cells through JNK phosphorylation. Molecular biology reports 10 19267218
2023 CircSLC39A8 attenuates paclitaxel resistance in ovarian cancer by regulating the miR‑185‑5p/BMF axis. Translational oncology 9 37499410
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 Alternative Transplantation With Post-Transplantation Cyclophosphamide in Aplastic Anemia: A Retrospective Report From the BMF-WG of Hunan Province, China. Transplantation and cellular therapy 8 36272527
2025 Bcl-2 modifying factor (Bmf): "a mysterious stranger" in the Bcl-2 family proteins. Cell death and differentiation 6 40849581
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 6 36315357
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
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
2024 Pressure loading regulates the stemness of liver cancer stem cells via YAP/BMF signaling axis. Journal of cellular physiology 3 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 3 35171055
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
2026 DNTTIP1 drives leukaemogenesis through MiDAC-mediated epigenetic silencing of BMF. Clinical and translational medicine 1 41603084
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
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