Affinage

MAFB

Transcription factor MafB · UniProt Q9Y5Q3

Length
323 aa
Mass
35.8 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 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

MAFB is a bZIP transcription factor that homodimerizes through its leucine zipper to bind Maf-recognition elements (MAREs) and heterodimerizes selectively with Fos but not Jun, acting as a context-dependent transcriptional activator on MARE-containing promoters (PMID:7935473). It functions as a master determinant of the monocyte/macrophage program: forced expression drives myeloblasts into mature macrophages while a dominant-negative allele blocks the monocytic fate (PMID:10790365), and within hematopoietic stem cells MAFB restrains M-CSF-driven myeloid commitment by antagonizing PU.1, which itself directly binds MAFB to inhibit its activity (PMID:19632180, PMID:15598817). MAFB output is tuned by a network of upstream inputs—TFE3, vitamin D3/Hox-A10, C/EBPβ isoform ratio, IL-10/STAT3, PGE2/EP4, and positive autoregulation—that converge on its promoter and protein level (PMID:19332055, PMID:18832725, PMID:19440205, PMID:24472656, PMID:34774558, PMID:10721736). In differentiated macrophages MAFB enforces an anti-inflammatory, tissue-repair phenotype: it directly drives complement C1q to enable efferocytosis (PMID:29167450), promotes M2 polarization and cholesterol-efflux machinery (PMID:28790455), sustains p62 to suppress NLRP3 inflammasome activation through mitophagy (PMID:37845329), and is required for monocyte-to-interstitial-macrophage specification (PMID:36928411). Beyond myeloid cells, MAFB is an essential developmental and homeostatic regulator: it controls podocyte differentiation and renal integrity by directly activating Nephrin and related genes (PMID:16847325, PMID:12217315, PMID:24722438), cooperates with Gcm2 to drive PTH expression and parathyroid morphogenesis (PMID:21713993), governs pancreatic alpha-cell glucagon production via Arx and islet beta-cell gene programs through ChIP-defined targets Pdx1, Nkx6.1 and GLUT2 (PMID:29378833, PMID:17360442), and establishes lymphatic endothelial identity downstream of VEGF-C/VEGFR-3 by inducing PROX1 (PMID:26549461, PMID:32307629). MAFB activity is modulated post-translationally by SUMOylation at K32/K297, which dampens transactivation and gates v-Myb repression (PMID:17548468), and by GSK3β- and proteasome-dependent turnover (PMID:29980194). MAFB also partners with chromatin and signaling factors—the MLL3/4 H3K4 methyltransferase complex in beta-cells (PMID:26180087), TET2 with the glucocorticoid receptor in tolerogenic dendritic cells (PMID:34893889), and ETS2 with PCAF/P300 to amplify oncogenic Notch1 signaling in T-ALL (PMID:29138297). Loss-of-function MAFB mutations cause multicentric carpotarsal osteolysis and skew human macrophage polarization (PMID:28093525).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    Established the fundamental biochemistry of MAFB—how it recognizes DNA and chooses dimerization partners—defining it as a bZIP transcriptional activator with oncogenic potential.

    Evidence DNA-binding, dimerization, reporter, and transformation assays in fibroblasts

    PMID:7935473

    Open questions at the time
    • Did not establish physiological target genes or in vivo function
    • Partner selectivity (Fos vs Jun) consequences not yet linked to a cellular program
  2. 1996 High

    Showed MAFB acts not only through MAREs but by direct protein interference with another transcription factor, repressing Ets-1 to block erythroid differentiation, revealing a dual transactivator/repressor mode.

    Evidence Yeast one-hybrid screen, co-IP, reporter assays, erythroblast differentiation readout

    PMID:8620536

    Open questions at the time
    • Mechanism of interaction domain not fully resolved
    • Relevance to native erythropoiesis in vivo untested
  3. 2000 High

    Defined MAFB as a specific and essential instructor of the macrophage fate, moving it from a biochemical entity to a lineage master regulator.

    Evidence Retroviral gain-of-function and dominant-negative in chicken myeloid precursors with morphology, marker, phagocytosis and NO readouts

    PMID:10790365

    Open questions at the time
    • Direct transcriptional targets driving the macrophage program not identified
    • Did not address mammalian HSC-level regulation
  4. 2004 High

    Identified PU.1 as a direct MAFB-binding antagonist and ERK as an inducer, placing MAFB within signaling-controlled fate-choice circuits in myeloid and megakaryocytic lineages.

    Evidence Direct binding assays, reporter assays, DC/macrophage and megakaryocyte differentiation systems

    PMID:15121870 PMID:15598817

    Open questions at the time
    • Stoichiometry and structural basis of PU.1-MAFB interaction unresolved
    • ERK-to-MAFB induction mechanism indirect (Medium-confidence megakaryocyte arm)
  5. 2006 High

    Extended the protein-interference mechanism to bone, showing MAFB blocks osteoclastogenesis by binding and disabling c-Fos, Mitf and NFATc1, while C/EBPβ isoform ratio and mTOR set MAFB levels upstream.

    Evidence Gain/loss-of-function in marrow macrophages, DNA-binding interference, reporter assays; C/EBPβ-null and LIP knock-in mice with rapamycin

    PMID:17158225 PMID:19440205

    Open questions at the time
    • Whether interference is competitive DNA occupancy or sequestration not fully dissected
    • C/EBPβ regulation single-lab (Medium)
  6. 2007 High

    Demonstrated MAFB is post-translationally gated by SUMOylation at K32/K297, which restrains transactivation and is the obligate substrate for v-Myb repression, adding a regulatory layer over its differentiation activity.

    Evidence In vitro SUMOylation, K32R/K297R mutagenesis, inducible Myb, differentiation and reporter assays

    PMID:17548468

    Open questions at the time
    • SUMO E3 ligase and deSUMOylating enzyme unidentified
    • Physiological signals controlling MAFB SUMO state unknown
  7. 2007 High

    Provided direct ChIP evidence that MAFB binds endocrine pancreas genes (Pdx1, Nkx6.1, GLUT2), establishing it as a developmental regulator of islet beta-cell gene programs.

    Evidence MafB knockout mouse, immunohistochemistry, ChIP on endogenous control regions

    PMID:17360442

    Open questions at the time
    • Did not separate developmental from adult beta-cell requirements
    • Functional consequence on insulin secretion not fully resolved
  8. 2009 High

    Revealed that MAFB (with c-Maf) enforces terminal differentiation by suppressing self-renewal, and that it restrains HSC myeloid commitment via PU.1, linking lineage choice to proliferative arrest.

    Evidence MafB/c-Maf double-KO with KLF4/c-Myc shRNA epistasis; MafB-deficient single-cell HSC analysis, competitive repopulation and serial transplantation

    PMID:19632180 PMID:19892988

    Open questions at the time
    • How MAFB transcriptionally represses KLF4/c-Myc not defined
    • Direct vs indirect control of M-CSFR sensitivity unresolved
  9. 2002 High

    Identified MAFB as essential for podocyte maturation downstream of Pod1, establishing a non-hematopoietic developmental role and a basis for glomerular disease.

    Evidence kr(enu) mouse, proteinuria, EM of foot processes, Podocin/Nephrin analysis, Pod1 epistasis; mafB/GFP knock-in null with renal and macrophage phenotypes

    PMID:12217315 PMID:16847325

    Open questions at the time
    • Direct podocyte target genes not yet defined at this stage
    • Tubular apoptosis mechanism unclear
  10. 2011 High

    Showed MAFB cooperates physically with Gcm2 to drive PTH expression and is required for parathyroid morphogenesis, defining a tissue-specific transcriptional partnership.

    Evidence MafB KO mouse, Co-IP of MafB and Gcm2, PTH promoter reporter, serum PTH/calcium

    PMID:21713993

    Open questions at the time
    • Interaction interface and DNA co-occupancy not structurally defined
    • Broader parathyroid target set unmapped
  11. 2014 High

    Defined MAFB as the macrophage effector of multiple homeostatic and anti-atherogenic programs—LXR/RXR→AIM survival, podocyte Nephrin protection, and IL-10/STAT3→MMP9/IL-7R—showing direct MARE-mediated target activation in disease contexts.

    Evidence Mafb-deficient mice with hematopoietic reconstitution, foam-cell apoptosis assays, podocyte-specific transgenics in diabetes, EMSA/reporter on MMP9 and IL-7R promoters; limb-bud ChIP-seq for Fos/Jun heterodimer-dependent p63/p73

    PMID:24445679 PMID:24472656 PMID:24722438 PMID:25005477

    Open questions at the time
    • Several arms single-lab (Medium)
    • How partner choice (Fos vs Jun) is set in vivo not resolved
    • Direct vs indirect target distinctions vary by study
  12. 2015 High

    Connected MAFB to chromatin-modifying machinery and a new lineage—showing it associates with MLL3/4 H3K4 methyltransferase complexes in beta-cells and is induced by VEGF-C to drive lymphatic PROX1 identity.

    Evidence Mass-spec pulldown and size fractionation of MLL3/4 complexes with NCOA6 knockdown; CAGE-seq of VEGF-C-induced LECs with Mafb-null lymphatic phenotype

    PMID:26180087 PMID:26549461

    Open questions at the time
    • Whether MAFB recruits MLL3/4 to specific loci genome-wide not shown
    • VEGF-C-to-MAFB induction mechanism (Medium) indirect
  13. 2016 High

    Demonstrated MAFB necessity/sufficiency for epidermal differentiation and direct hormonal/lncRNA control of its expression, broadening it to a general epithelial and developmental differentiation regulator.

    Evidence Epidermal ChIP-seq with ANCR/TINCR knockdown and TF rescue; AR ChIP on Mafb 3'UTR AREs with KO genital phenotype; PRLR-conditional KO linking gestational beta-cell MafB; SUMO-K32→CDK6 in colorectal cancer

    PMID:25805135 PMID:26636186 PMID:27217483 PMID:27829226

    Open questions at the time
    • Tissue-specific cofactor logic distinguishing epidermal vs other programs not unified
    • SUMO/CDK6 and PRLR arms single-lab (Medium)
  14. 2018 High

    Identified MAFB as a protein-stability-regulated oncogenic cofactor—stabilized by GSK3β inhibition/proteasome blockade and partnering with ETS2/PCAF/P300 to amplify Notch1 in T-ALL—linking its turnover to cancer phenotypes.

    Evidence GSK3β/proteasome inhibitor immunoblotting in myeloma; Co-IP of MAFB-ETS2 and MAFB-PCAF/P300 with knockdown in T-ALL; conditional alpha-cell KO defining glucagon/Arx control; Sox10 regulation in cardiac neural crest

    PMID:29138297 PMID:29378833 PMID:29980194 PMID:30236445

    Open questions at the time
    • E3 ligase mediating MAFB ubiquitination unidentified
    • Several arms single-lab (Medium)
  15. 2021 High

    Integrated MAFB into prostaglandin and tolerogenic signaling axes, showing PGE2/EP4 induces it for macrophage anti-inflammatory repair and GR/TET2 partnering drives tolDC DNA-demethylation programs.

    Evidence Parallel myeloid COX-2/EP4/MafB KO mice in acute kidney injury; Co-IP of GR-MAFB-TET2 with bisulfite sequencing and ChIP in human DCs

    PMID:34774558 PMID:34893889

    Open questions at the time
    • How MAFB-TET2 selects loci for demethylation not fully defined
    • Direct vs indirect anti-/pro-inflammatory targets downstream of EP4 not enumerated
  16. 2023 High

    Established MAFB's role in tissue-resident macrophage specification and innate-immune restraint, showing it controls monocyte-to-interstitial-macrophage transition and sustains p62/mitophagy to suppress the NLRP3 inflammasome.

    Evidence Lung IM niche depletion model with scRNA-seq and chimeras; MafB KO/knockdown macrophages with NLRP3 assays, mitochondrial ROS, and myeloid KO mice challenged with LPS/P. aeruginosa

    PMID:36928411 PMID:37845329

    Open questions at the time
    • Transcriptional target driving p62 expression not directly mapped
    • Selectivity for NLRP3 over other inflammasomes mechanistically incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MAFB's partner selection, SUMO state, and proteasomal turnover are coordinately set to specify which tissue-specific gene program it executes remains unresolved.
  • No identified E3 ligase or SUMO ligase/protease that controls MAFB in vivo
  • No structural model of MAFB heterodimer or cofactor (MLL3/4, TET2, ETS2) complexes
  • Logic determining activator vs repressor (DNA-binding interference) mode across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 7 R-HSA-168256 Immune System 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-4839726 Chromatin organization 2
Partners
EP300ETS1ETS2FOSGCM2NCOA6PU.1TET2
Complex memberships
MAFB-GR-TET2 complexMLL3/MLL4 H3K4 methyltransferase complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 MafB physically interacts with Ets-1 via its basic region or leucine-zipper domain (identified by yeast one-hybrid screen with DNA-bound Ets-1), and represses Ets-1 transactivation of synthetic promoters containing Ets binding sites as well as the endogenous transferrin receptor gene, thereby inhibiting erythroid differentiation. Yeast one-hybrid screen, co-immunoprecipitation/pulldown, transient transfection reporter assays, overexpression in erythroblast cell line with transferrin receptor gene readout Cell High 8620536
1994 MafB forms homodimers through its leucine zipper, binds Maf-recognition elements (MAREs), forms heterodimers with v-Maf and Fos but not Jun, and acts as a transcriptional activator of MARE-containing promoters; overexpression transforms chicken embryo fibroblasts. DNA-binding assays, dimerization assays, transient cotransfection reporter assays, focus formation/transformation assays Molecular and cellular biology High 7935473
2000 MafB overexpression in transformed chicken hematopoietic myeloblasts drives rapid macrophage differentiation (morphology, surface markers, phagocytic activity, nitric oxide release), while a dominant-negative MafB allele inhibits myeloid colony formation and myeloblast-to-macrophage differentiation, establishing MafB as a specific and essential determinant of the monocytic program. Retroviral overexpression and dominant-negative allele in transformed chicken hematopoietic precursors, colony assays, morphology, surface marker expression, phagocytosis and NO-release functional assays The EMBO journal High 10790365
2007 MafB directly regulates transcription of Pdx1, Nkx6.1, and GLUT2 in developing islet beta-cells, as demonstrated by ChIP showing MafB binding within endogenous control region sequences of these genes; MafB-null embryos have reduced insulin+ and glucagon+ cells with normal total endocrine cell numbers. MafB knockout mouse analysis, immunohistochemistry, ChIP on endogenous gene control regions Proceedings of the National Academy of Sciences of the United States of America High 17360442
2006 MafB negatively regulates RANKL-induced osteoclast differentiation: MafB proteins physically interfere with the DNA-binding ability of c-Fos, Mitf, and NFATc1, inhibiting their transactivation of NFATc1 and OSCAR; overexpression blocks TRAP+ multinuclear osteoclast formation while retaining phagocytic activity; RNAi knockdown of MafB enhances osteoclastogenesis. Overexpression and RNAi in bone marrow-derived monocyte/macrophage cells, TRAP staining, reporter assays, DNA-binding interference assays Blood High 17158225
2007 SUMO-1 modifies MafB in vitro and in vivo at lysines K32 and K297. SUMOylation reduces MafB-driven transactivation and macrophage differentiation potential; SUMOylation-deficient MafB (K32R K297R) resists v-Myb-mediated repression and can drive macrophage differentiation even in the presence of active Myb. Direct repression of MafB transactivation by v-Myb is strictly dependent on MafB SUMO modification. In vitro SUMOylation assay, site-directed mutagenesis (K32R K297R), inducible Myb alleles, macrophage differentiation assays, transactivation reporter assays Molecular and cellular biology High 17548468
2009 Combined deficiency of MafB and c-Maf enables self-renewal of mature monocytes and macrophages without loss of differentiated phenotype; this continuous proliferation requires concomitant upregulation of pluripotent stem cell factors KLF4 and c-Myc, as shown by shRNA inactivation. MafB/c-Maf double-knockout, shRNA knockdown of KLF4 and c-Myc, in vitro expansion, transplantation assays Science High 19892988
2009 MafB specifically restricts M-CSF-mediated myeloid commitment divisions in hematopoietic stem cells (HSCs); MafB deficiency enhances HSC sensitivity to M-CSF and activates PU.1 in HSCs in vivo; single-cell analysis shows reduced MafB enables M-CSF to instruct asymmetric divisions producing PU.1+ progeny; competitive repopulation advantage is PU.1 and M-CSF-receptor dependent. MafB-deficient mouse model, single-cell analysis, competitive repopulation assays, serial transplantation, in vivo M-CSF receptor signaling analysis Cell High 19632180
2004 PU.1 directly binds MafB protein, inhibits its transcriptional activity in macrophages, and represses its ability to induce macrophage differentiation; high PU.1 activity favors DC fate by inhibiting both expression and activity of MafB, while constitutive MafB expression inhibits DC differentiation. Activated transcription factors in transformed myeloid progenitors, direct protein binding assay between PU.1 and MafB, reporter assays for transcriptional activity, DC/macrophage differentiation assays Blood High 15598817
2004 ERK signaling induces MafB/Kreisler expression during megakaryocyte differentiation; MafB synergizes with GATA and Ets factors to enhance transcription from the GPIIb (CD41) proximal promoter; dominant-negative or antisense suppression of MafB inhibits ERK-dependent GPIIb transactivation. ERK activation assays, dominant-negative and antisense MafB constructs, luciferase reporter assays with GPIIb promoter, cotransfection with GATA/Ets Molecular and cellular biology Medium 15121870
2006 MafB is essential for podocyte differentiation and renal tubule survival; MafB-null mice show renal dysgenesis with abnormal podocyte differentiation, tubular apoptosis, and suppressed F4/80 expression in nonadherent macrophages; F4/80 expression is directly regulated by MafB in hematopoietic cells. mafB/GFP knock-in null mutant mouse, histology, immunofluorescence, primary culture of fetal liver hematopoietic cells Molecular and cellular biology High 16847325
2002 MafB/Kreisler is essential for cellular differentiation of glomerular visceral epithelial cells (podocytes); homozygous kr(enu) mice develop proteinuria, foot process fusion/effacement, and reduced Podocin and Nephrin levels; MafB acts downstream of Pod1 bHLH transcription factor during the capillary loop to mature stage transition. kr(enu) homozygous mouse model, histology, proteinuria measurement, electron microscopy of podocyte foot processes, gene expression analysis, epistasis with Pod1 Developmental biology High 12217315
2011 MafB interacts directly with Gcm2 to synergistically activate PTH gene expression; MafB is required for parathyroid separation from the thymus and migration toward the thyroid; MafB deficiency impairs PTH expression and secretion, reduces renal cyp27b1 expression, and reduces bone mineralization. MafB knockout mouse, co-immunoprecipitation of MafB and Gcm2, luciferase reporter assay for PTH promoter, histology, serum PTH/calcium measurements Journal of bone and mineral research High 21713993
2014 MafB mediates oxidized LDL-activated LXR/RXR-induced expression of apoptosis inhibitor of macrophages (AIM) in foam cells; without MafB, activated LXR/RXR fails to induce AIM expression; Mafb-deficient macrophages are prone to apoptosis and haematopoietic reconstitution with Mafb-deficient cells reduces early atherogenic lesion. Mafb-deficient mouse, hematopoietic reconstitution in LDL receptor-deficient mice, foam cell apoptosis assays, LXR/RXR activation experiments, gene expression analysis Nature communications High 24445679
2017 MafB is a critical transcriptional regulator of complement component C1q in macrophages; Mafb-deficient macrophages have reduced C1q expression and impaired efferocytosis; efferocytosis defect can be rescued by wild-type but not C1q-deficient mouse serum; MafB overexpression induces C1q-dependent gene expression; Mafb deficiency increases glomerular autoimmunity. Mafb-deficient mouse, hemolysis assay for classical complement pathway, efferocytosis rescue experiments with serum from WT vs C1q-deficient mice, MafB overexpression, immunohistochemistry Nature communications High 29167450
2015 MLL3 and MLL4 histone H3K4 methyltransferase complexes physically bind MAFB (and closely related MAFA) in islet beta-cells; MAFB was found in ~1.5 MDa MLL3/MLL4 complexes by size fractionation; knockdown of NCOA6 (core MLL3/4 subunit) reduces expression of MAFA and MAFB target genes in mouse and human beta-cell lines. Unbiased in-cell biochemical pulldown plus mass spectrometry, size-fractionation of beta-cell extracts, NCOA6 knockdown in mouse and human beta-cell lines, gene expression analysis Diabetes High 26180087
2009 TFE3 transcription factor directly transactivates the MAFB promoter through an E-box element conserved across mammalian species; EMSA identified the TFE3-binding site in the MAFB promoter; deletion or mutation of this E-box prevents TFE3-driven transactivation; TFE3 overexpression highly induces MAFB in human hematopoietic cells undergoing macrophage differentiation. EMSA with MAFB promoter E-box probe, luciferase reporter assay with E-box deletion/mutation constructs, TFE3 retroviral overexpression and siRNA knockdown in human hematopoietic cells Experimental cell research Medium 19332055
2008 Vitamin D3 induces monocyte differentiation via a sequential transactivation cascade: VDR → Hox-A10 → MafB; Hox-A10 directly binds to the MafB promoter (demonstrated by EMSA and luciferase assay) and upregulates MafB expression, which in turn drives monocyte differentiation of CD34+ hematopoietic progenitors. Retroviral Hox-A10 transduction of CD34+ progenitors, EMSA with MafB promoter probe, luciferase reporter assay, vitamin D3 stimulation with RT-PCR for Hox-A10 and MafB Journal of immunology Medium 18832725
2000 The mouse mafB gene promoter contains Hox-A10-binding palindromic MARE/E-box elements and GC-boxes; the gene is positively auto-regulated by MafB itself (cotransfection assay); MyoD activates the mafB promoter; the gene lacks intron structure. Genomic cloning, RNase protection for transcription start site mapping, transient transfection luciferase reporter assays with 5'-flanking region deletions/mutations Gene Medium 10721736
2003 In the developing chick hindbrain, MafB exhibits positive autoregulatory activity, represses Hoxb1 expression, and can synergize with or antagonize Krox20 activity in a spatially restricted manner; the kreisler mutation also causes ectopic MafB activation in rhombomere 3. Gain-of-function electroporation in chick embryo hindbrain, re-analysis of kreisler mutant mice, in situ hybridization Developmental biology Medium 12490204
2000 FGF signaling regulates MafB/kr expression in the hindbrain; exogenous FGFs induce ectopic mafB/kr expression while an FGF signaling inhibitor specifically downregulates mafB/kr in the hindbrain neuroepithelium and neural crest. Exogenous FGF protein application to chick neural tube, FGF signaling inhibitor treatment, in situ hybridization for mafB/kr Development Medium 11044406
1998 MafB/Kr expression in rhombomeres 5/6 is regulated by a posteriorizing signal present in posterior somites; retinoic acid mimics this effect, repressing MafB/Kr in r5/6 and inducing it more rostrally in a concentration-dependent manner, indicating that a threshold concentration of a posteriorizing morphogen (retinoic acid or related signal) defines the MafB/Kr expression domain. Quail/chick chimera grafting of rhombomeres and somites, retinoic acid bead implantation, in situ hybridization for MafB/Kr Development Medium 9477316
2014 In developing chick limb buds, MafB/cFos heterodimers repress apoptosis while MafB/cJun heterodimers promote apoptosis; MafB and cJun directly activate expression of p63 and p73 (cell cycle arrest components) as demonstrated by ChIP-seq in chick limb buds. ChIP-seq in chick limb buds, gain-of-function overexpression of MafB/cFos and MafB/cJun heterodimers, apoptosis quantification, functional promoter analysis of p63 and p73 Development Medium 25005477
2016 MAFB is necessary and sufficient for epidermal progenitor differentiation; MAF:MAFB regulates ~393 genes in epidermis; ANCR and TINCR lncRNAs act as upstream regulators of MAF:MAFB; ChIP-seq showed MAF:MAFB binding to epidermal differentiation TF genes (GRHL3, ZNF750, KLF4, PRDM1) whose expression they control; these downstream TFs rescue specific MAF:MAFB target gene subsets upon MAF:MAFB loss. Kinetic transcriptome analysis, ChIP-seq, lncRNA knockdown (ANCR, TINCR), TF rescue experiments, gain-of-function and loss-of-function of MAF/MAFB Developmental cell High 25805135
2016 Androgen receptor (AR) signaling is required for Mafb expression in male genital tubercle mesenchyme; two functional androgen response elements (AREs) were identified in the Mafb 3'UTR and shown to bind AR; β-catenin also regulates Mafb expression during urethral masculinization; Mafb KO male mice exhibit defective embryonic urethral formation. Mafb KO mouse, AR KO mouse, exogenous androgen treatment, luciferase reporter assay with Mafb 3'UTR AREs, ChIP for AR binding at 3'UTR AREs, immunohistochemistry Endocrinology Medium 26636186
2009 C/EBPβ isoform ratio regulates osteoclastogenesis through MafB: the long transactivating LAP isoform promotes MafB promoter activity and MafB gene expression (attenuating osteoclastogenesis), while the short repressive LIP isoform reduces MafB; rapamycin (mTOR inhibitor) increases LAP/LIP ratio and inhibits osteoclastogenesis via MafB in a C/EBPβ-dependent manner. C/EBPβ null and LIP knock-in mouse osteoclast precursors, rapamycin treatment, MafB promoter reporter assays with LAP and LIP constructs, qRT-PCR for MafB expression The EMBO journal Medium 19440205
2014 MafB directly regulates Nephrin transcription in podocytes (shown by reporter assay); podocyte-specific MafB overexpression in diabetic mice ameliorates albuminuria and preserves Nephrin expression; Mafb overexpression also upregulates glutathione peroxidase and enhances Notch2 expression in podocytes. Podocyte-specific MafB transgenic mice with streptozotocin-induced diabetes, luciferase reporter assay for Nephrin promoter, histology, urine/serum biochemistry Journal of the American Society of Nephrology Medium 24722438
2014 MafB is a downstream target of the IL-10/STAT3 signaling pathway in macrophages; IL-10-activated STAT3 induces MafB, which in turn directly activates MMP9 and IL-7R gene transcription through MARE elements in their promoters (demonstrated by EMSA and luciferase reporter assay). MafB inactivation and overexpression in human primary macrophages, EMSA with MMP9 and IL-7R promoter MARE probes, luciferase reporter assay, IL-10/STAT3 pathway inhibition Biochimica et biophysica acta Medium 24472656
2017 MAFB knockdown impairs acquisition of the anti-inflammatory profile of human M-CSF-driven macrophages and establishes the MAFB-dependent gene signature; macrophages from patients with multicentric carpotarsal osteolysis (caused by MAFB mutations) show skewed polarization, validating the MAFB anti-inflammatory role in human disease. MAFB siRNA knockdown in human monocyte-derived macrophages, gene expression profiling, functional polarization assays, analysis of patient macrophages with MAFB mutations Journal of immunology Medium 28093525
2022 MAFB acts in synergy with glucocorticoid receptor (GR) to drive tolerogenic DC differentiation; GR and MAFB both interact with methylcytosine dioxygenase TET2 and bind to genomic loci that undergo specific demethylation in tolDCs; MAFB knockdown erases tolerogenic properties of tolDCs, reverses specific DNA demethylation, and reverts MAFB-dependent gene upregulation. Transcriptomic and epigenomic analysis, MAFB knockdown in human DCs, Co-IP of GR, MAFB, and TET2, ChIP for genomic binding, bisulfite sequencing for DNA methylation Nucleic acids research High 34893889
2018 MAFB enhances oncogenic Notch1 signaling in T-ALL by binding ETS2 and recruiting acetyltransferases PCAF and P300; MAFB and ETS2 synergistically enhance Notch1 signaling; MAFB knockdown reduces Notch1 target genes MYC and HES1 expression and impairs T-ALL growth. Gain-of-function screen in mouse T-ALL models, Co-IP for MAFB-ETS2 and MAFB-PCAF/P300 interactions, MAFB knockdown in mouse and human T-ALL cells, Notch target gene expression analysis Science signaling High 29138297
2016 SUMOylation of MAFB at lysine 32 by SUMO1 is critical for cell cycle regulation in colorectal cancer cells; SUMOylated MAFB directly binds the CDK6 promoter to regulate CDK6 transcription; MAFB knockdown blocks CRC cell proliferation by G0/G1 arrest; K32-mutant MAFB (non-SUMOylatable) shows reduced tumorigenic capacity in xenografts. SUMO1 SUMOylation assay, ChIP for MAFB binding to CDK6 promoter, shRNA knockdown, cell cycle analysis, K32 mutation, xenograft mouse model Oncotarget Medium 27829226
2018 GSK3β activity and proteasome activity regulate MAFb protein stability (not mRNA level); inhibition of GSK3β or treatment with proteasome inhibitors (bortezomib, carfilzomib) prevents MAFb protein degradation; MAFb is constitutively degraded by the ubiquitin/proteasome system, and high MAFb protein confers resistance to proteasome inhibitors in multiple myeloma cells. GSK3β inhibitor treatment, proteasome inhibitor treatment, immunoblotting for MAFb protein vs mRNA, MAFb silencing by lentiviral knockdown, apoptosis/caspase activation assays BMC cancer Medium 29980194
2018 MafB is a critical transcriptional regulator of glucagon production and secretion in adult mouse alpha-cells; endocrine cell-specific and tamoxifen-inducible MafB knockout mice show decreased Arx+glucagon+ cells and glucagon content; MafB regulates Arx expression; MafB-null islets fail to respond to arginine due to impaired arginine transporter gene expression. Conditional and inducible MafB knockout mice, immunohistochemistry, gene expression analysis, glucagon secretion assays with arginine challenge Molecular and cellular biology High 29378833
2015 MAFB is rapidly induced and activated by VEGF-C/VEGFR-3 signaling in lymphatic endothelial cells (LECs); MAFB induces PROX1 expression and other markers of differentiated LECs; Mafb-null embryos show impaired lymphatic patterning in the skin. CAGE RNA-seq for VEGF-C-induced transcriptional changes in LECs, Mafb global knockout mouse analysis of lymphatic patterning, MAFB knockdown in LECs Cell reports Medium 26549461
2020 Lymphatic endothelial cell (LEC)-intrinsic MAFB controls lymphatic vascular morphogenesis; conditional lymphatic-specific Mafb knockout produces embryonic lymphatic patterning defects and increased branching postnatally; loss of lymphatic MAFB enhances tumor-induced lymphangiogenesis. Conditional lymphatic-specific Mafb knockout (Cre-lox), histological analysis of lymphatic vessels, tumor lymphangiogenesis model Angiogenesis Medium 32307629
2021 PGE2-mediated EP4 receptor activation induces MafB expression in kidney macrophages following acute injury; myeloid Mafb deletion recapitulates myeloid COX-2 or EP4 deletion, with delayed recovery, persistent pro-inflammatory macrophages, and increased kidney fibrosis; MafB upregulates anti-inflammatory genes and suppresses pro-inflammatory genes downstream of COX-2/PGE2/EP4. Myeloid-specific COX-2 KO, EP4 KO, and MafB KO mice, acute kidney injury model, macrophage phenotyping, gene expression analysis Kidney international High 34774558
2023 MafB controls the transition from Ly6C+ monocyte local proliferation to interstitial macrophage (IM) subset specification in the lung; MafB-deficient monocytes fail to properly differentiate into IMs after niche engraftment; c-Maf specifically regulates CD206+ IM subset identity. Inducible lung IM niche depletion/refilling model, time-course single-cell RNA-seq, bone marrow chimeras, MafB conditional gene targeting Nature immunology High 36928411
2023 MafB sustains p62 expression in macrophages to inhibit NLRP3 inflammasome activation; MafB knockdown/knockout markedly enhances NLRP3 (but not NLRP1, NLRC4, or AIM2) inflammasome activation; MafB inhibits mitochondrial damage and mitochondrial ROS production; LPS-induced MafB downregulation accelerates NLRP3 activation; myeloid MafB-deficient mice show increased systemic IL-1β. MafB KO and knockdown macrophages, NLRP3 inflammasome activation assays, p62 expression analysis, mitochondrial ROS measurement, myeloid-specific MafB KO mice with in vivo LPS/P. aeruginosa challenge Communications biology High 37845329
2018 MafB acts as a transcriptional regulator of Sox10 expression specifically in the cardiac neural crest; loss of MafB function in chick cardiac neural crest reduces Sox10 expression without affecting other neural crest subpopulations. Transcriptome analysis of isolated cardiac neural crest, functional MafB knockdown in chick cardiac neural crest, in situ hybridization for Sox10 Developmental biology Medium 30236445
2016 PRLR signaling in maternal beta-cells during pregnancy is required for transient gestational MafB expression; conditional beta-cell-specific PRLR deletion abolishes gestational MafB induction; beta-cell-specific MafB deletion produces gestational diabetes mellitus with inadequate beta-cell expansion and failure to induce PRLR-dependent proliferation genes. Floxed Prlr conditional KO, MafB conditional beta-cell KO, pregnancy model, beta-cell mass quantification, gene expression analysis (Foxm1, cyclins, Tph1, serotonin) Diabetes Medium 27217483
2019 Maf and Mafb repress SST+ interneuron generation from MGE secondary progenitors; postnatal conditional deletion shows distinct roles of Mafb (morphological maturation) vs c-Maf in cortical interneuron development; Maf and Mafb positively regulate Mef2c and Snap25 to drive interneuron morphological maturation. Conditional MGE-specific single and double Mafb/c-Maf knockout mice, single-cell gene expression analysis, electrophysiology, morphological analysis Cell reports Medium 30699346
2017 MafB directly up-regulates key cellular mediators of cholesterol efflux from macrophage foam cells; MafB promotes macrophage M2 polarization; MafB expression is up-regulated by metabolic/immunological stimuli that promote M2 polarization or cholesterol efflux; MafB is downregulated by miR-155 and miR-33. MafB overexpression and knockdown in macrophages, cholesterol efflux assays, M2 marker expression, systems biology analysis of MafB target genes Scientific reports Medium 28790455

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation. Cell 255 8620536
2006 A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. Developmental biology 240 16580660
2009 MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science (New York, N.Y.) 237 19892988
2000 MafB is an inducer of monocytic differentiation. The EMBO journal 237 10790365
2006 MafB negatively regulates RANKL-mediated osteoclast differentiation. Blood 221 17158225
1994 MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun. Molecular and cellular biology 211 7935473
2007 MafB is required for islet beta cell maturation. Proceedings of the National Academy of Sciences of the United States of America 199 17360442
2010 MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes 198 20627934
2006 MafB is essential for renal development and F4/80 expression in macrophages. Molecular and cellular biology 177 16847325
2011 MafA and MafB activity in pancreatic β cells. Trends in endocrinology and metabolism: TEM 172 21719305
2006 MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells. Diabetes 166 16443760
2015 A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation. Developmental cell 162 25805135
2004 Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate. Blood 151 15598817
2009 MafB restricts M-CSF-dependent myeloid commitment divisions of hematopoietic stem cells. Cell 140 19632180
2016 Gestational Diabetes Mellitus From Inactivation of Prolactin Receptor and MafB in Islet β-Cells. Diabetes 116 27217483
2009 Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis through MafB. The EMBO journal 112 19440205
2022 Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway. Frontiers in immunology 104 35237277
2017 The transcription factor MafB promotes anti-inflammatory M2 polarization and cholesterol efflux in macrophages. Scientific reports 100 28790455
2002 The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells. Developmental biology 98 12217315
2014 MafB promotes atherosclerosis by inhibiting foam-cell apoptosis. Nature communications 93 24445679
2023 MafB-restricted local monocyte proliferation precedes lung interstitial macrophage differentiation. Nature immunology 90 36928411
2001 Ectopic expression of MAFB gene in human myeloma cells carrying (14;20)(q32;q11) chromosomal translocations. Japanese journal of cancer research : Gann 79 11429052
1997 The expression pattern of the mafB/kr gene in birds and mice reveals that the kreisler phenotype does not represent a null mutant. Mechanisms of development 79 9256349
2017 MafB is a critical regulator of complement component C1q. Nature communications 74 29167450
2016 Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects. American journal of human genetics 69 27181683
2000 Hindbrain patterning: FGFs regulate Krox20 and mafB/kr expression in the otic/preotic region. Development (Cambridge, England) 66 11044406
2023 Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer's disease-specific cis-regulatory elements. Cell genomics 65 36950385
1998 Defined concentrations of a posteriorizing signal are critical for MafB/Kreisler segmental expression in the hindbrain. Development (Cambridge, England) 62 9477316
2017 MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis. Journal of immunology (Baltimore, Md. : 1950) 60 28093525
2018 A mutation in transcription factor MAFB causes Focal Segmental Glomerulosclerosis with Duane Retraction Syndrome. Kidney international 59 29779709
2019 Role of MafB in macrophages. Experimental animals 58 31582643
2014 Sexually dimorphic expression of Mafb regulates masculinization of the embryonic urethral formation. Proceedings of the National Academy of Sciences of the United States of America 58 25362053
2003 Novel activities of Mafb underlie its dual role in hindbrain segmentation and regional specification. Developmental biology 56 12490204
2015 Integration of Cistromic and Transcriptomic Analyses Identifies Nphs2, Mafb, and Magi2 as Wilms' Tumor 1 Target Genes in Podocyte Differentiation and Maintenance. Journal of the American Society of Nephrology : JASN 55 25556170
2020 Loss of the transcription factor MAFB limits β-cell derivation from human PSCs. Nature communications 53 32488111
2015 MLL3 and MLL4 Methyltransferases Bind to the MAFA and MAFB Transcription Factors to Regulate Islet β-Cell Function. Diabetes 53 26180087
2019 MiR-320a induces diabetic nephropathy via inhibiting MafB. Aging 51 31102503
2015 The MAFB transcription factor impacts islet α-cell function in rodents and represents a unique signature of primate islet β-cells. American journal of physiology. Endocrinology and metabolism 50 26554594
2019 Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function. Cell reports 49 30699346
2017 Hyperlipidemia-Induced MicroRNA-155-5p Improves β-Cell Function by Targeting Mafb. Diabetes 48 28970282
2018 Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. Glia 47 30485546
2011 MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 47 21713993
2008 Identification of primary MAFB target genes in multiple myeloma. Experimental hematology 46 19013005
2015 MiR-223 targeting MAFB suppresses proliferation and migration of nasopharyngeal carcinoma cells. BMC cancer 45 26055874
2004 Extracellular signal-regulated kinase induces the megakaryocyte GPIIb/CD41 gene through MafB/Kreisler. Molecular and cellular biology 45 15121870
2018 MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic α Cells In Vivo. Molecular and cellular biology 44 29378833
2007 Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice. Developmental biology 44 18199433
2020 MAFB Promotes Cancer Stemness and Tumorigenesis in Osteosarcoma through a Sox9-Mediated Positive Feedback Loop. Cancer research 43 32234710
2016 Transcription Factor MafB Coordinates Epidermal Keratinocyte Differentiation. The Journal of investigative dermatology 43 27208706
2004 The recurrent translocation t(14;20)(q32;q12) in multiple myeloma results in aberrant expression of MAFB: a molecular and genetic analysis of the chromosomal breakpoint. British journal of haematology 43 15257707
2015 DeepCAGE Transcriptomics Reveal an Important Role of the Transcription Factor MAFB in the Lymphatic Endothelium. Cell reports 39 26549461
2006 Expression of a novel gene, MafB, in Dupuytren's disease. The Journal of hand surgery 39 16473681
2018 Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally. Diabetes 38 30425060
2007 SUMO modification regulates MafB-driven macrophage differentiation by enabling Myb-dependent transcriptional repression. Molecular and cellular biology 38 17548468
2020 miR-155 Knockdown Protects against Cerebral Ischemia and Reperfusion Injury by Targeting MafB. BioMed research international 37 32090104
1999 Human KRML (MAFB): cDNA cloning, genomic structure, and evaluation as a candidate tumor suppressor gene in myeloid leukemias. Genomics 36 10444328
2002 Characterization of the chicken L-Maf, MafB and c-Maf in crystallin gene regulation and lens differentiation. Genes to cells : devoted to molecular & cellular mechanisms 34 12081646
2014 Overexpression of Mafb in podocytes protects against diabetic nephropathy. Journal of the American Society of Nephrology : JASN 33 24722438
2021 Myeloid cyclooxygenase-2/prostaglandin E2/E-type prostanoid receptor 4 promotes transcription factor MafB-dependent inflammatory resolution in acute kidney injury. Kidney international 32 34774558
2022 Coordinated glucocorticoid receptor and MAFB action induces tolerogenesis and epigenome remodeling in dendritic cells. Nucleic acids research 31 34893889
2020 Lymphatic MAFB regulates vascular patterning during developmental and pathological lymphangiogenesis. Angiogenesis 31 32307629
2016 Differential expression patterns of MafB and c-Maf in macrophages in vivo and in vitro. Biochemical and biophysical research communications 31 26996125
2011 Reexpression of oncoprotein MafB in proliferative β-cells and Men1 insulinomas in mouse. Oncogene 31 22120711
2020 Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation. eLife 30 32452758
2020 RECQL4, Negatively Regulated by miR-10a-5p, Facilitates Cell Proliferation and Invasion via MAFB in Ovarian Cancer. Frontiers in oncology 30 33014878
2006 Enhanced expression of MafB inhibits macrophage apoptosis induced by cigarette smoke exposure. American journal of respiratory cell and molecular biology 30 17079784
2020 MAFB and MAF Transcription Factors as Macrophage Checkpoints for COVID-19 Severity. Frontiers in immunology 29 33312178
2014 MafB is a downstream target of the IL-10/STAT3 signaling pathway, involved in the regulation of macrophage de-activation. Biochimica et biophysica acta 29 24472656
2020 MicroRNA-148a facilitates inflammatory dendritic cell differentiation and autoimmunity by targeting MAFB. JCI insight 28 32213710
2018 MAFb protein confers intrinsic resistance to proteasome inhibitors in multiple myeloma. BMC cancer 28 29980194
2015 Beta-cell regeneration from vimentin+/MafB+ cells after STZ-induced extreme beta-cell ablation. Scientific reports 27 26129776
2015 MAFB as a novel regulator of human adipose tissue inflammation. Diabetologia 26 26115698
2014 Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis. Development (Cambridge, England) 26 25005477
2015 Androgen Regulates Mafb Expression Through its 3'UTR During Mouse Urethral Masculinization. Endocrinology 25 26636186
2009 Neither MafA/L-Maf nor MafB is essential for lens development in mice. Genes to cells : devoted to molecular & cellular mechanisms 25 19624757
2008 The vitamin D3/Hox-A10 pathway supports MafB function during the monocyte differentiation of human CD34+ hemopoietic progenitors. Journal of immunology (Baltimore, Md. : 1950) 25 18832725
2018 Transcriptome profiling of the cardiac neural crest reveals a critical role for MafB. Developmental biology 24 30236445
2016 MafB deficiency accelerates the development of obesity in mice. FEBS open bio 24 27419056
2000 Molecular cloning and functional characterization of the mouse mafB gene. Gene 24 10721736
2011 High MafB expression following burn augments monocyte commitment and inhibits DC differentiation in hemopoietic progenitors. Journal of leukocyte biology 23 21984745
2020 Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis. Kidney international 22 32622525
2019 MafB Is Important for Pancreatic β-Cell Maintenance under a MafA-Deficient Condition. Molecular and cellular biology 22 31208980
2016 SUMOylated MAFB promotes colorectal cancer tumorigenesis. Oncotarget 21 27829226
2015 Association of polymorphisms in the MAFB gene and the risk of coronary artery disease and ischemic stroke: a case-control study. Lipids in health and disease 21 26204962
2016 Transcription Factor MafB Promotes Hepatocellular Carcinoma Cell Proliferation through Up-Regulation of Cyclin D1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 27448450
2023 Inhibition of LXR controls the polarization of human inflammatory macrophages through upregulation of MAFB. Cellular and molecular life sciences : CMLS 19 36930354
2022 MAFA and MAFB regulate exocytosis-related genes in human β-cells. Acta physiologica (Oxford, England) 19 34978761
2018 MiRNA-199a-5p positively regulated RANKL-induced osteoclast differentiation by target Mafb protein. Journal of cellular biochemistry 19 30387167
2015 Fratricide activity of MafB protein of N. meningitidis strain B16B6. BMC microbiology 19 26242409
2010 c-Maf and MafB transcription factors are differentially expressed in Huxley's and Henle's layers of the inner root sheath of the hair follicle and regulate cuticle formation. Journal of dermatological science 19 20060689
2009 TFE3 transcription factor regulates the expression of MAFB during macrophage differentiation. Experimental cell research 19 19332055
2016 The role of macrophage transcription factor MafB in atherosclerotic plaque stability. Atherosclerosis 18 27214395
2019 Transcription factor MafB is a marker of tumor-associated macrophages in both mouse and humans. Biochemical and biophysical research communications 17 31679694
2017 Transcription factor MafB may play an important role in secondary hyperparathyroidism. Kidney international 17 28964572
2017 MAFB enhances oncogenic Notch signaling in T cell acute lymphoblastic leukemia. Science signaling 17 29138297
2015 DNMT3A R882 mutation is associated with elevated expression of MAFB and M4/M5 immunophenotype of acute myeloid leukemia blasts. Leukemia & lymphoma 17 25721756
2023 MafB regulates NLRP3 inflammasome activation by sustaining p62 expression in macrophages. Communications biology 16 37845329
2019 Loss of MafA and MafB expression promotes islet inflammation. Scientific reports 16 31235823
2014 Generation of insulin-producing cells from the mouse liver using β cell-related gene transfer including Mafa and Mafb. PloS one 16 25397325
2021 Periodontitis Risk Variants at SIGLEC5 Impair ERG and MAFB Binding. Journal of dental research 15 34852650

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