Affinage

MAF

Transcription factor Maf · UniProt O75444

Length
373 aa
Mass
38.5 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

c-MAF is a large Maf-family bZIP transcription factor that functions as a lineage-determining regulator across multiple cell types, directing T helper subset specification (Th2, Tfh, Tr1, Tγδ17, iTreg), macrophage identity and polarization, lens fiber cell differentiation, epidermal progenitor differentiation, and liver sinusoidal endothelial cell specification (PMID:8674125, PMID:10403649, PMID:30538336, PMID:29414937, PMID:35364013, PMID:25805135). It binds MARE (Maf recognition element) sequences as a homodimer or heterodimer with partners such as AhR, SOX9, and Nrf2, employing a DNA-sequence-dependent conformational change in its basic region that enables recognition of extended GC-flanking sequences distinct from canonical bZIP elements (PMID:11179227, PMID:19797082, PMID:17875642). c-MAF directly transactivates key target genes—including IL-4, IL-10, IL-21, crystallins, cyclin D2, integrin β7, F4/80, and Csf-1r—and can also remodel chromatin by recruiting Pax6, CREB, Brg1/Snf2h at crystallin loci or by promoting chromatin accessibility at Rorc and Blk loci in γδ T cells (PMID:8674125, PMID:19414776, PMID:20676095, PMID:16675956, PMID:30538336). Its stability and output are tuned by GSK-3 phosphorylation (which enhances transcriptional activity via P/CAF recruitment while triggering proteasomal degradation), by SUMOylation (which suppresses IL-21 transactivation through Daxx/HDAC2 recruitment), and by ubiquitin-dependent turnover mediated by the E3 ligase HERC4 and opposed by deubiquitinases Otub1, USP7, and USP5 (PMID:18042454, PMID:30059018, PMID:26825710, PMID:32842143, PMID:31822558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1996 High

    Establishing c-Maf as a T cell transcription factor answered whether a bZIP protein could directly activate the IL-4 promoter, founding the concept that Maf factors control cytokine gene transcription.

    Evidence EMSA/footprinting plus reporter and ectopic expression in Th1/B cells

    PMID:8674125

    Open questions at the time
    • No in vivo loss-of-function evidence at this stage
    • Whether c-Maf is sufficient for IL-4 in a physiological context was untested
    • Mechanism of cooperation with NFAT was not structurally resolved
  2. 1999 High

    Germline knockouts demonstrated that c-Maf is essential in vivo for both IL-4 production in CD4+ T cells and for lens fiber cell differentiation, establishing it as a lineage-determining factor in two unrelated tissues.

    Evidence c-maf−/− mice with cytokine measurement and lens histology/crystallin expression analysis

    PMID:10383433 PMID:10403649

    Open questions at the time
    • Redundancy with MafB in macrophages/other tissues not addressed
    • Cell-intrinsic versus microenvironmental contributions to T cell phenotype not dissected
    • Conditional KO needed to exclude developmental versus functional roles
  3. 2001 High

    Biophysical analysis revealed that Maf proteins recognize extended MARE elements through a DNA-sequence-dependent conformational folding mechanism in the basic region, distinguishing them from canonical bZIP factors and explaining their unique target selectivity.

    Evidence Secondary structure analysis, trypsin sensitivity, binding affinity/dissociation measurements, and DNA contact mapping

    PMID:11179227

    Open questions at the time
    • Full crystal structure of c-Maf itself not yet available (MafG structure came later)
    • How conformational change integrates with heterodimer partners was unknown
  4. 2001 High

    Interaction studies with Hox proteins and c-Myb showed that c-Maf's bZIP domain serves as a protein-interaction platform for both cooperative and inhibitory partnerships, broadening the model beyond simple DNA binding.

    Evidence Phage display, Co-IP, domain mutagenesis, EMSA, and transformation assays (Hox); Co-IP and differentiation assays (c-Myb)

    PMID:10477683 PMID:11036080

    Open questions at the time
    • Structural basis of Hox-bZIP interaction unresolved
    • Physiological relevance of Hox-Maf antagonism in vivo not tested
  5. 2002 High

    Identification of the c-Maf–SOX9 interaction and synergistic activation of Col2a1 extended c-Maf's role into chondrogenesis and revealed that bZIP–HMG box hetero-partnerships drive cartilage gene expression.

    Evidence Yeast two-hybrid, Co-IP, GST pull-down, domain mapping, luciferase reporter

    PMID:12381733

    Open questions at the time
    • In vivo cartilage phenotype of c-Maf loss not demonstrated
    • Whether SOX9 interaction is required for all chondrocyte targets unclear
  6. 2005 High

    Discovery that c-MAF transactivates cyclin D2, integrin β7, and ARK5 in myeloma provided the molecular basis for its oncogenic function—driving proliferation, adhesion, and invasion in t(14;16) myeloma.

    Evidence ChIP, reporter assays with MARE mutation, dominant-negative inhibition, xenograft tumor model, invasion assay

    PMID:14998494 PMID:16044163

    Open questions at the time
    • Relative contribution of individual targets to in vivo myeloma progression not dissected
    • Whether c-MAF-driven myeloma depends on the same ubiquitin regulatory axis was unknown
  7. 2006 High

    ChIP studies at crystallin loci in lens revealed that c-Maf cooperates with Pax6 and CREB to recruit chromatin remodelers Brg1 and Snf2h, showing it acts as a chromatin organizer, not just a classical transactivator.

    Evidence ChIP in lens chromatin, reporter assays in lens explants, transgenic reporter mice

    PMID:16675956

    Open questions at the time
    • Whether c-Maf directly recruits Brg1/Snf2h or does so indirectly was unresolved
    • Genome-wide chromatin remodeling by c-Maf in lens not profiled
  8. 2007 High

    GSK-3 phosphorylation was shown to create a dual switch—enhancing c-Maf transcriptional activity via P/CAF coactivator recruitment while simultaneously marking it for ubiquitin-proteasomal degradation—explaining how Maf protein turnover couples to peak transcriptional output.

    Evidence In vitro kinase assay, phosphosite mutagenesis, Co-IP with P/CAF, ubiquitination assay

    PMID:18042454

    Open questions at the time
    • Specific E3 ligase recognizing phosphorylated Maf not identified at this point
    • Whether the same mechanism applies to c-Maf versus MafA in all tissues was unclear
  9. 2009 High

    Structural determination of the MafG–DNA complex and SPR binding studies with Nrf2–MafG heterodimers resolved how Maf basic-region residues (Arg57, Asn61) recognize flanking GC sequences and how a single residue difference (Ala-502 in Nrf2 vs. Tyr in Maf) dictates differential MARE binding specificity.

    Evidence X-ray crystallography of MafG–DNA, mutagenesis, surface plasmon resonance-microarray

    PMID:17875642 PMID:19797082

    Open questions at the time
    • Crystal structure of full-length c-Maf or c-Maf homodimer on DNA still lacking
    • Structural basis of Maf–CNC heterodimer selectivity on endogenous chromatin unresolved
  10. 2009 High

    Demonstrating that combined MafB and c-Maf deficiency enables macrophage self-renewal (via KLF4/c-Myc upregulation) without dedifferentiation revealed that large Maf factors function as anti-proliferative gatekeepers in terminally differentiated macrophages.

    Evidence MafB/c-Maf double-knockout macrophages, shRNA knockdown of KLF4/c-Myc, in vivo transplantation

    PMID:19892988

    Open questions at the time
    • Whether the self-renewal phenotype is tumor-prone in vivo was not assessed
    • Relative individual contributions of MafB versus c-Maf to the anti-proliferative block were not fully separated
  11. 2009 High

    c-Maf was shown to directly transactivate IL-10 via MARE binding in a STAT3-dependent manner during Th17 polarization, and with AhR to co-activate IL-10 and IL-21 for Tr1 cells, expanding its cytokine repertoire beyond IL-4 and linking it to anti-inflammatory T cell programs.

    Evidence Retroviral transduction, MARE binding assay, STAT3 KO analysis, AhR Co-IP, reporter assay, EAE model

    PMID:19414776 PMID:20676095

    Open questions at the time
    • Genome-wide target overlap between Th2 and Tr1 c-Maf programs not mapped
    • Whether AhR–c-Maf interaction is direct or bridged by DNA was not structurally resolved
  12. 2015 High

    ChIP-seq and epistasis experiments established MAF and MAFB as master regulators of epidermal progenitor differentiation, binding upstream of 393 differentiation genes and key TFs (GRHL3, ZNF750, KLF4, PRDM1), while the lncRNA linc-MAF-4 was shown to recruit LSD1/EZH2 to repress MAF transcription in Th1 cells.

    Evidence ChIP-seq, RNA-seq, knockdown/overexpression, RIP with LSD1/EZH2, 3C chromatin interaction assay

    PMID:25621826 PMID:25805135

    Open questions at the time
    • Mechanism by which ANCR/TINCR control MAF/MAFB expression not fully dissected
    • Whether linc-MAF-4 regulation operates in non-T cell contexts unknown
  13. 2016 High

    Identification of HERC4 as the E3 ubiquitin ligase for c-Maf (polyubiquitinating K85 and K297), and USP5 as its opposing deubiquitinase, provided the first defined writer-eraser pair controlling c-Maf stability in myeloma.

    Evidence Affinity chromatography/MS, Co-IP, ubiquitination assay with lysine mutagenesis, xenograft model

    PMID:26825710

    Open questions at the time
    • Whether HERC4 recognizes GSK-3-phosphorylated c-Maf specifically was not tested
    • Role of HERC4 in non-myeloma c-Maf-expressing cells unknown
  14. 2018 High

    Conditional knockouts in γδ T cells and Treg cells revealed that c-Maf is a universal fate switch for Tγδ17 commitment (by promoting Rorc chromatin accessibility and antagonizing TCF1) and for RORγt+FOXP3+ iTreg differentiation and IL-10 production, with its loss causing spontaneous colitis.

    Evidence Conditional KO in γδ and Treg lineages, ATAC-seq, antigen-specific T cell tracking, colitis scoring

    PMID:29414937 PMID:30538336

    Open questions at the time
    • Direct c-Maf binding sites at Rorc locus not mapped by ChIP
    • Whether c-Maf–TCF1 antagonism involves direct physical interaction or indirect competition was unresolved
  15. 2018 High

    SUMOylation of c-Maf was shown to differentially regulate target gene selection: SUMO modification recruits Daxx/HDAC2 to specifically repress Il21 while sparing other targets, and SUMO-deficient c-Maf preferentially activates Il21 via enhanced CBP/p300-mediated acetylation.

    Evidence Transgenic NOD mice expressing WT versus SUMO-mutant c-Maf, ChIP for Daxx/HDAC2/CBP/p300, pharmacological CBP inhibition

    PMID:30059018

    Open questions at the time
    • Whether SUMOylation affects other c-Maf targets beyond Il21 was not comprehensively tested
    • The SUMO E3 ligase responsible for c-Maf SUMOylation in T cells was not identified
  16. 2020 High

    Myeloid-specific c-Maf deletion showed it controls M2 macrophage polarization by binding the Csf-1r conserved noncoding sequence and by acting as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, linking transcriptional identity to metabolic programming.

    Evidence Myeloid conditional KO, ChIP at Csf-1r, metabolomics, T cell suppression assay, tumor model

    PMID:31945018

    Open questions at the time
    • Mechanism by which c-Maf directly controls metabolic enzyme expression not detailed
    • Whether metabolic effects are cell-autonomous or secondary to Csf-1r regulation was not fully dissected
  17. 2021 High

    Identification of Otub1 and USP7 as additional deubiquitinases that stabilize c-Maf (removing K48-linked chains) completed a multi-enzyme regulatory network controlling c-Maf abundance, particularly in myeloma.

    Evidence MS interactome, Co-IP, ubiquitination assays with mutagenesis, xenograft models

    PMID:31822558 PMID:32842143

    Open questions at the time
    • Hierarchical or redundant relationships among USP5, USP7, and Otub1 not established
    • Tissue-specific usage of different DUBs for c-Maf regulation unknown
  18. 2022 High

    Endothelium-specific deletion showed c-Maf is a critical postnatal switch for liver sinusoidal endothelial cell identity, with enforced expression sufficient to activate the sinusoidal transcriptional program in generic endothelial cells.

    Evidence scRNA-seq, endothelium-specific conditional KO, c-Maf overexpression in human ECs, hepatocyte co-culture

    PMID:35364013

    Open questions at the time
    • Upstream signals inducing c-Maf specifically in liver sinusoidal endothelium not identified
    • Direct genomic targets of c-Maf in sinusoidal endothelium not mapped by ChIP-seq
  19. 2024 High

    TGF-β was shown to induce Tfh fate through c-Maf independently of Bcl6, establishing c-Maf as a cell-fate switch between Tfh and Th17 in TGF-β-rich environments and dissociating the long-assumed Bcl6 requirement for CXCR5 induction.

    Evidence In vitro Tfh differentiation, c-Maf and Bcl6 conditional KO comparison, CXCR5 reporter, in vivo validation

    PMID:38427718

    Open questions at the time
    • Whether c-Maf directly binds CXCR5 regulatory elements was not shown
    • How c-Maf integrates TGF-β and TCR signals to decide between Tfh and Th17 fate at the single-cell level remains unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive understanding of how c-Maf selects among its diverse target genes in different lineages—whether through combinatorial partner usage, chromatin context, or post-translational modification state—remains to be integrated into a unified model.
  • No genome-wide c-Maf ChIP-seq across multiple cell types exists for systematic comparison
  • Crystal structure of c-Maf homodimer or c-Maf–partner heterodimer on DNA has not been determined
  • SUMO E3 ligase and site-specific kinase crosstalk in non-myeloma contexts remain uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-168256 Immune System 6 R-HSA-1266738 Developmental Biology 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 2 R-HSA-4839726 Chromatin organization 2
Partners
AHRDAXXHERC4OTUB1PAX6SOX9USP5USP7

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 c-Maf is a basic region/leucine zipper transcription factor that binds to a c-Maf response element (MARE) in the proximal IL-4 promoter and transactivates IL-4 gene expression; it acts in synergy with NF-ATp to initiate endogenous IL-4 production. EMSA/footprinting, transactivation reporter assays, ectopic expression in Th1 cells and B cells Cell High 8674125
1999 c-Maf has a critical and selective function in IL-4 gene transcription in vivo; c-maf−/− mice show markedly deficient IL-4 production in CD4+ T cells and NK T cells, but normal IL-13 and IgE levels. Germline knockout mouse, cytokine measurement by ELISA/intracellular staining Immunity High 10403649
1999 c-Maf is indispensable for lens fiber cell differentiation in mice; c-maf null embryos lack normal lenses and show severe impairment of crystallin gene expression. Targeted gene disruption (knockout mouse), histology, lacZ reporter knockin The Journal of biological chemistry High 10383433
2009 c-Maf directly transactivates IL-10 gene expression through binding to a MARE motif in the IL-10 promoter during Th17 polarization; this induction depends on STAT3. Retroviral transduction, MARE binding assay, reporter assay, STAT3 knockout analysis Journal of immunology High 19414776
2010 AhR binds directly to c-Maf and promotes transactivation of the Il10 and Il21 promoters synergistically, driving Tr1 cell development in response to IL-27. Co-immunoprecipitation (AhR-c-Maf interaction), reporter assay, AhR ligand manipulation, EAE model Nature immunology High 20676095
2004 c-Maf transactivates the cyclin D2 promoter to enhance myeloma proliferation; it also drives integrin β7 expression to promote myeloma adhesion to bone marrow stroma and increase VEGF production. Gene expression profiling, reporter assay (cyclin D2 promoter), dominant-negative inhibition, xenograft tumor model Cancer cell High 14998494
2007 GSK-3 phosphorylates Maf (and MafA sequentially on S61, T57, T53, S49), increasing transcriptional activity through recruitment of coactivator P/CAF while also triggering ubiquitination and proteasomal degradation; P/CAF protects MafA from ubiquitination. In vitro kinase assay, mutagenesis of phosphorylation sites, microarray, Co-IP, ubiquitination assay Molecular cell High 18042454
2009 Crystal structure of MafG-DNA complex reveals that Arg57 and Asn61 in the basic region make critical contacts with extended GC sequences of the MARE, defining an alternative bZIP DNA recognition mechanism. X-ray crystallography of MafG-DNA complex, mutagenesis Molecular and cellular biology High 19797082
2007 Nrf2-MafG heterodimer and MafG homodimer bind the consensus MARE with high affinity but show differential binding to degenerate sequences; Ala-502 in Nrf2 (versus Tyr in Maf) is the critical determinant of this binding specificity difference. Surface plasmon resonance-microarray, mutagenesis (Nrf2 A502Y), target gene expression analysis The Journal of biological chemistry High 17875642
2001 DNA sequence-dependent folding of both the basic and ancillary DNA-binding regions of Maf is required for MARE recognition; two basic region residues (not conserved in canonical bZIP proteins) facilitate the conformational change enabling extended DNA element binding. Secondary structure analysis, trypsin sensitivity, binding affinity/dissociation rate measurements, DNA contact analysis The EMBO journal High 11179227
2009 Combined deficiency of MafB and c-Maf enables self-renewal of mature macrophages without loss of differentiated function; this proliferation requires upregulation of KLF4 and c-Myc (demonstrated by shRNA knockdown). Double-knockout mouse, shRNA knockdown of KLF4/c-Myc, in vivo transplantation Science High 19892988
2016 HERC4 is an E3 ubiquitin ligase that interacts with c-Maf, catalyzes its polyubiquitination at K85 and K297, and promotes its proteasomal degradation; the deubiquitinase USP5 reverses this polyubiquitination. Affinity chromatography, mass spectrometry, Co-IP, ubiquitination assay, mutagenesis, xenograft tumor model Blood High 26825710
2021 Otub1 (OTU family deubiquitinase) interacts with c-Maf, removes K48-linked polyubiquitin chains to prevent its degradation, and enhances its transcriptional activity; this depends on Otub1 Lys71 and its N-terminus but is independent of UBE2O. Mass spectrometry interactome, Co-IP, ubiquitination assay, mutagenesis, xenograft model Blood High 32842143
2019 USP7 interacts with c-Maf, MafA, and MafB, blocks their polyubiquitination and degradation, and promotes their transcriptional activity in myeloma cells. Mass spectrometry, Co-IP, ubiquitination assay, knockdown, luciferase reporter The Journal of biological chemistry High 31822558
2014 c-MAF ubiquitination is mediated by multiple lysine residues; K85 and K350 are sufficient but not the sole sites; c-MAF is also degraded via the lysosomal pathway. Mutagenesis (K→R substitutions), ubiquitination assay, luciferase reporter, mRNA/protein expression The international journal of biochemistry & cell biology Medium 25448412
2010 KSHV-encoded miRNAs silence MAF in endothelial cells, revealing MAF as a transcriptional repressor that maintains lymphatic endothelial cell (LEC) identity by suppressing blood endothelial cell (BEC)-specific genes. miRNA target validation, gene expression profiling, loss-of-function in LEC Genes & development Medium 20080955
2002 A new long form of c-Maf (Lc-Maf) interacts with SOX9 through its bZIP domain (interacting with SOX9's HMG box), and they synergistically activate the type II collagen (Col2a1) gene promoter. Yeast two-hybrid, Co-IP, GST pull-down, domain mapping, luciferase reporter, in situ hybridization The Journal of biological chemistry High 12381733
2001 Hox proteins (Hoxd12 and MHox/Prx1) interact with c-Maf through its bZIP domain and the homeodomain of Hox, inhibiting c-Maf DNA binding, transcriptional activation, and transforming activity. Phage display, Co-IP, domain mutagenesis, EMSA, transactivation reporter, transformation assay The Journal of biological chemistry High 11036080
1999 c-Maf physically interacts with c-Myb in myeloid cells to form inhibitory complexes; elevated c-Maf drives monocytic differentiation and eventual apoptosis through inhibition of c-Myb targets (Bcl-2, CD13/APN). Inducible c-Maf overexpression in bipotent myeloid progenitor lines, Co-IP (c-Maf/c-Myb), differentiation assays Blood Medium 10477683
2000 v-Maf binds as a homodimer to a variant MARE between -66 and -54 in the mouse p53 promoter and transactivates p53 expression; overexpression of v-Maf in primary cells leads to p53-dependent cell death. EMSA, reporter assay, overexpression in primary cells, p53-null rescue experiment The Journal of biological chemistry Medium 10747965
2006 Pax6 and c-Maf co-bind the alphaA-crystallin locus in lens chromatin; high alphaA-crystallin expression correlates with increased c-Maf and CREB binding to the promoter and histone H3K9 hyperacetylation; c-Maf regulates chromatin-remodeling enzymes Brg1 and Snf2h at the locus. Chromatin immunoprecipitation (ChIP), reporter assays in lens explants, transgenic reporter mice The EMBO journal High 16675956
2009 c-Maf directly regulates F4/80 expression in macrophages by binding to a half-MARE site in the F4/80 promoter, as demonstrated by luciferase reporter and EMSA; c-maf null macrophages lose F4/80 expression but retain Mac-1. c-Maf knockout mouse, luciferase reporter, EMSA Gene Medium 19539733
2012 c-Maf is required for development of dorsal horn laminae III/IV neurons and for proper differentiation of MafA+/Ret+/GFRα2+ low-threshold mechanoreceptors in DRG; c-Maf loss compromises central and peripheral projections of mechanoreceptive afferents. c-Maf conditional knockout mouse, marker gene expression analysis, axon projection tracing The Journal of neuroscience High 22514301
2015 MAF and MAFB are necessary and sufficient for epidermal progenitor differentiation; they regulate 393 differentiation genes and bind (ChIP-seq) to known epidermal TF genes (GRHL3, ZNF750, KLF4, PRDM1) acting upstream of these factors; lncRNAs ANCR and TINCR are essential upstream regulators of MAF:MAFB. ChIP-seq, transcriptome profiling (RNA-seq), knockdown/overexpression, epistasis rescue experiments Developmental cell High 25805135
2018 c-Maf is a universal transcription factor required for Tγδ17 cell commitment in the thymus; it promotes chromatin accessibility and expression of Rorc and Blk, while antagonizing TCF1 to prevent Tγδ1 (IFN-γ) fate; γδTCR signal strength tunes c-Maf expression. c-Maf conditional knockout in γδ T cells, ATAC-seq (chromatin accessibility), gene expression, epistasis with TCF1 Nature immunology High 30538336
2018 c-MAF inactivation in Treg cells impairs differentiation and IL-10 production of bacteria-specific iTreg cells, causing accumulation of colitogenic Th17 cells and spontaneous colitis; c-MAF is required for RORγt+FOXP3+ Treg identity and function. Treg-specific c-MAF conditional knockout, microbiota-specific T cell tracking, IL-10 measurement, colitis scoring Nature High 29414937
2020 c-Maf controls immunosuppressive macrophage (M2) polarization; it has direct binding sites in the Csf-1r gene conserved noncoding sequence; it also acts as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis to promote M2 polarization. c-Maf myeloid-specific conditional knockout, ChIP (Csf-1r), metabolomics, T cell suppression assay, tumor growth models The Journal of clinical investigation High 31945018
2022 c-Maf induction in endothelial cells is a critical postnatal switch for liver sinusoidal identity; endothelium-specific deletion of c-Maf disrupts sinusoidal development, expands postnatal hematopoiesis, and increases pro-fibrotic sensitivity; enforced c-Maf expression in generic endothelial cells activates a liver sinusoidal transcriptional program. scRNA-seq, endothelium-specific conditional KO, c-Maf overexpression in human ECs, functional hepatocyte co-culture Cell stem cell High 35364013
2021 MAF activates β/γ-crystallin expression in high myopia by directly binding crystallin gene promoters and by activating TGF-β1-Smad signaling, establishing a MAF-TGF-β1-crystallin axis in pathological lens growth. Reporter assay (crystallin promoters), ChIP, Smad signaling assays, myopia mouse models Nature communications Medium 33833231
2018 SUMOylation of c-Maf suppresses IL-21 transactivation; SUMO-defective c-Maf preferentially transactivates Il21 by inhibiting Daxx/HDAC2 recruitment to the Il21 promoter and enhancing CBP/p300-mediated histone acetylation. Transgenic NOD mice (WT vs. SUMOylation-mutant c-Maf), ChIP (Daxx/HDAC2/CBP/p300), luciferase reporter, CBP30 pharmacological inhibition The Journal of clinical investigation High 30059018
2021 c-MAF controls perivascular macrophage identity across multiple organs; myeloid-specific c-MAF deletion ablates LYVE1+/Folate receptor 2+/CD38+ perivascular macrophages and alters adipose tissue vascular branching; this population regulates metabolic syndrome. c-MAF myeloid conditional KO, flow cytometry, scRNA-seq, HFD metabolic phenotyping Science immunology High 34597123
2015 Linc-MAF-4 is a chromatin-associated lncRNA that associates with LSD1 and EZH2 chromatin modifiers through long-range chromatin interactions to repress MAF transcription in Th1 cells; linc-MAF-4 knockdown skews T cell differentiation toward the Th2 phenotype. RNA-seq, 3C/chromatin interaction assay, RIP (LSD1/EZH2), linc-MAF-4 knockdown in primary human T cells Nature immunology High 25621826
2012 Bcl6 and c-Maf cooperate in human Tfh cell differentiation: Bcl6 controls migration genes (CXCR4, CXCR5, CCR7) and T-B interaction molecules, while c-Maf induces IL-21 expression and CXCR5; coexpression reveals cooperative regulation of CXCR4, PD-1, and ICOS. Retroviral transduction of Bcl6 and/or Maf in primary human CD4+ T cells, gene expression profiling Journal of immunology Medium 22427637
2011 IL-2 drives c-MAF expression in human CD4+ T cells through STAT5 binding to specific sites in the C-MAF promoter, as demonstrated by ChIP; IL-2R blockade significantly inhibits TCR-induced c-MAF expression and downstream IL-4 production. ChIP (STAT5 at C-MAF promoter), daclizumab/JAK3 inhibitor treatment, cytokine measurement Journal of immunology Medium 21876034
2005 ARK5 is a direct transcriptional target of c-MAF and MAFB; c-MAF binds to MARE sequences in the ARK5 promoter (ChIP), and ARK5 mediates IGF-1-induced myeloma cell invasion. ChIP, reporter assay with MARE mutation/deletion, gene expression induction by c-MAF/MAFB overexpression, invasion assay Oncogene Medium 16044163
2001 c-Maf and Jun share downstream target genes required for cell transformation; transactivation through MARE is necessary for Maf-induced transformation; heterodimer formation with other bZIP factors is not required for transformation. Leucine zipper swap experiments, chimeric repressor (Mxi1-Sin3 domain), transformation assays in chicken embryo fibroblasts The Journal of biological chemistry Medium 11461901
2019 CRISPR-mediated deletion of MAF in Tph cells abrogates their ability to induce memory B cell differentiation into plasmablasts in vitro, indicating MAF is required for Tph cell helper function via IL-21. CRISPR KO of MAF in primary human Tph cells, B cell differentiation co-culture assay, IL-21 neutralization JCI insight Medium 31536480
2017 TCF-1 limits Tc17 (CD8+ IL-17-producing) cell development by sequentially suppressing MAF and RORγt expression in double-positive thymocytes, and TCF-1 ablation results in enhanced Tc17 differentiation. TCF-1 conditional KO, chromatin state analysis, gene expression profiling in thymocytes The Journal of experimental medicine Medium 31142588
2024 TGF-β induces Tfh cell fate in CD4+ T cells through c-Maf; TGF-β-induced CXCR5 expression requires c-Maf but is independent of Bcl6; c-Maf acts as a cell-fate switch between Tfh and Th17 in TGF-β-rich environments. In vitro Tfh differentiation protocol, c-Maf conditional KO, Bcl6 KO comparison, CXCR5 reporter, in vivo validation Science immunology High 38427718
2015 FGF signaling upregulates c-Maf expression via an FGF2-responsive element (FRE) in the c-Maf promoter containing AP-1 and Ets-binding sites; c-Jun and Etv5/ERM (nuclear effectors of ERK1/2) bind these regions in lens chromatin; FGF signaling also upregulates αA-crystallin directly and indirectly via c-Maf. ChIP (c-Jun, Etv5/ERM in lens), reporter assay, ERK1/2-deficient lens analysis The Journal of biological chemistry Medium 26719333

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nature immunology 622 20676095
1996 The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 539 8674125
2018 c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 419 29414937
2002 Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene 392 12234662
1995 Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins. Molecular and cellular biology 373 7623813
1998 Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma. Blood 326 9616139
1999 The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 317 10403649
2004 Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma. Cancer cell 306 14998494
2012 Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 299 22427637
2015 The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nature immunology 275 25621826
2019 PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI insight 246 31536480
1997 The world according to Maf. Nucleic acids research 237 9224592
2009 MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science (New York, N.Y.) 235 19892988
2003 The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila. Nature cell biology 233 14578908
1999 Regulation of lens fiber cell differentiation by transcription factor c-Maf. The Journal of biological chemistry 215 10383433
1994 MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun. Molecular and cellular biology 210 7935473
2009 c-Maf regulates IL-10 expression during Th17 polarization. Journal of immunology (Baltimore, Md. : 1950) 199 19414776
2016 Small Maf proteins (MafF, MafG, MafK): History, structure and function. Gene 198 27058431
1998 Multivalent DNA binding complex generated by small Maf and Bach1 as a possible biochemical basis for beta-globin locus control region complex. The Journal of biological chemistry 169 9565602
2015 A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation. Developmental cell 161 25805135
1998 Identification of Bach2 as a B-cell-specific partner for small maf proteins that negatively regulate the immunoglobulin heavy chain gene 3' enhancer. The EMBO journal 157 9755173
2020 Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer. The Journal of clinical investigation 146 31945018
2007 Small Maf proteins in mammalian gene control: mere dimerization partners or dynamic transcriptional regulators? Journal of molecular biology 131 18201722
2010 KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. Genes & development 129 20080955
2012 The small MAF transcription factors MAFF, MAFG and MAFK: current knowledge and perspectives. Biochimica et biophysica acta 127 22721719
2015 Transcription factors, CncC and Maf, regulate expression of CYP6BQ genes responsible for deltamethrin resistance in Tribolium castaneum. Insect biochemistry and molecular biology 116 26255690
2003 Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice. Neoplasia (New York, N.Y.) 104 12659668
2018 The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells. Nature immunology 103 30538336
2007 GSK-3-mediated phosphorylation enhances Maf-transforming activity. Molecular cell 99 18042454
2006 Regulation of alphaA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin. The EMBO journal 93 16675956
2007 Molecular basis distinguishing the DNA binding profile of Nrf2-Maf heterodimer from that of Maf homodimer. The Journal of biological chemistry 89 17875642
1997 Rat maf related genes: specific expression in chondrocytes, lens and spinal cord. Oncogene 88 9038383
2013 The p53 transcription factor modulates microglia behavior through microRNA-dependent regulation of c-Maf. Journal of immunology (Baltimore, Md. : 1950) 82 24319262
2012 Strontium ranelate rebalances bone marrow adipogenesis and osteoblastogenesis in senescent osteopenic mice through NFATc/Maf and Wnt signaling. Aging cell 82 22321691
2018 An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells. Nature immunology 81 30201991
2016 Linc-MAF-4 regulates Th1/Th2 differentiation and is associated with the pathogenesis of multiple sclerosis by targeting MAF. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 79 27756768
2020 CncC/Maf-mediated xenobiotic response pathway in insects. Archives of insect biochemistry and physiology 78 32281173
2023 Intestinal microbiota-specific Th17 cells possess regulatory properties and suppress effector T cells via c-MAF and IL-10. Immunity 77 38039966
2006 A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant "cerulean cataract" in an Indian family. American journal of medical genetics. Part A 76 16470690
2007 Multiple mechanisms and functions of maf transcription factors in the regulation of tissue-specific genes. Journal of biochemistry 70 17569705
2017 The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells. Frontiers in immunology 69 28496444
1999 c-Maf induces monocytic differentiation and apoptosis in bipotent myeloid progenitors. Blood 69 10477683
2009 Structural basis of alternative DNA recognition by Maf transcription factors. Molecular and cellular biology 68 19797082
2021 Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia. Nature communications 65 33833231
2005 ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma. Oncogene 60 16044163
2001 Interaction of Maf transcription factors with Pax-6 results in synergistic activation of the glucagon promoter. The Journal of biological chemistry 60 11457839
2016 The ubiquitin ligase HERC4 mediates c-Maf ubiquitination and delays the growth of multiple myeloma xenografts in nude mice. Blood 59 26825710
2002 A new long form of c-Maf cooperates with Sox9 to activate the type II collagen gene. The Journal of biological chemistry 59 12381733
2020 Malat1 Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells. Journal of immunology (Baltimore, Md. : 1950) 57 32321759
2001 A set of Hox proteins interact with the Maf oncoprotein to inhibit its DNA binding, transactivation, and transforming activities. The Journal of biological chemistry 56 11036080
2022 Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction. Cell stem cell 55 35364013
2017 Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes. Journal of immunology (Baltimore, Md. : 1950) 55 29127150
2020 c-MAF, a Swiss Army Knife for Tolerance in Lymphocytes. Frontiers in immunology 54 32117317
2003 The islet beta cell-enriched RIPE3b1/Maf transcription factor regulates pdx-1 expression. The Journal of biological chemistry 54 12551916
2001 Distinct roles of maf genes during Xenopus lens development. Mechanisms of development 54 11231068
2002 An IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines. Proceedings of the National Academy of Sciences of the United States of America 53 12271139
2011 Maf acts downstream of ComGA to arrest cell division in competent cells of B. subtilis. Molecular microbiology 52 21564336
2004 Roles of Maf family proteins in lens development. Developmental dynamics : an official publication of the American Association of Anatomists 52 14991699
2021 Targeting the Otub1/c-Maf axis for the treatment of multiple myeloma. Blood 51 32842143
2014 GSK3-mediated MAF phosphorylation in multiple myeloma as a potential therapeutic target. Blood cancer journal 50 24442204
2004 MafT, a new member of the small Maf protein family in zebrafish. Biochemical and biophysical research communications 50 15207702
1996 Transactivation activity of Maf nuclear oncoprotein is modulated by Jun, Fos and small Maf proteins. Oncogene 50 8552399
2021 c-MAF-dependent perivascular macrophages regulate diet-induced metabolic syndrome. Science immunology 48 34597123
2006 Cell context reveals a dual role for Maf in oncogenesis. Oncogene 48 16247450
2019 TCF-1 limits the formation of Tc17 cells via repression of the MAF-RORγt axis. The Journal of experimental medicine 47 31142588
2001 DNA sequence-dependent folding determines the divergence in binding specificities between Maf and other bZIP proteins. The EMBO journal 46 11179227
2015 Regulation of c-Maf and αA-Crystallin in Ocular Lens by Fibroblast Growth Factor Signaling. The Journal of biological chemistry 44 26719333
2021 Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF. The Journal of clinical investigation 43 34403373
2000 Maf transcriptionally activates the mouse p53 promoter and causes a p53-dependent cell death. The Journal of biological chemistry 43 10747965
2019 The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival. The Journal of biological chemistry 42 31822558
2019 A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation. Immunity 38 31422869
2007 Novel MAF mutation in a family with congenital cataract-microcornea syndrome. Molecular vision 38 17982426
2003 Pulverulent cataract with variably associated microcornea and iris coloboma in a MAF mutation family. The British journal of ophthalmology 38 12642301
2019 Mebendazole elicits potent antimyeloma activity by inhibiting the USP5/c-Maf axis. Acta pharmacologica Sinica 37 31197245
2006 Carcinogenesis and transcriptional regulation through Maf recognition elements. Cancer science 37 17129360
2017 Transcriptional Responses of Candida albicans to Antimicrobial Peptide MAF-1A. Frontiers in microbiology 36 28567034
2017 Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients. Leukemia 35 28745329
2012 c-Maf is required for the development of dorsal horn laminae III/IV neurons and mechanoreceptive DRG axon projections. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 22514301
2014 MAF mediates crosstalk between Ras-MAPK and mTOR signaling in NF1. Oncogene 33 24509877
1998 Lens-specific gene recruitment of zeta-crystallin through Pax6, Nrl-Maf, and brain suppressor sites. Molecular and cellular biology 33 9528779
2022 Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators? Frontiers in immunology 31 35359922
2014 Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature. American journal of medical genetics. Part A 31 24664492
1998 Rat maf-related factors: the specificities of DNA binding and heterodimer formation. Biochemical and biophysical research communications 31 9571165
1995 Transcriptional stimulation of the retina-specific QR1 gene upon growth arrest involves a Maf-related protein. Molecular and cellular biology 30 7565708
2020 MAFB and MAF Transcription Factors as Macrophage Checkpoints for COVID-19 Severity. Frontiers in immunology 29 33312178
2017 Specification and spatial arrangement of cells in the germline stem cell niche of the Drosophila ovary depend on the Maf transcription factor Traffic jam. PLoS genetics 29 28542174
2015 c-Maf regulates pluripotency genes, proliferation/self-renewal, and lineage commitment in ROS-mediated senescence of human mesenchymal stem cells. Oncotarget 29 26496036
2014 Ubiquitination of the transcription factor c-MAF is mediated by multiple lysine residues. The international journal of biochemistry & cell biology 29 25448412
2011 IL-2 regulates expression of C-MAF in human CD4 T cells. Journal of immunology (Baltimore, Md. : 1950) 28 21876034
2009 c-Maf is essential for the F4/80 expression in macrophages in vivo. Gene 28 19539733
2012 The tumor suppressor p53 regulates c-Maf and Prox-1 to control lens differentiation. Current molecular medicine 27 22827438
2024 TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf. Science immunology 25 38427718
2023 The role and regulation of Maf proteins in cancer. Biomarker research 25 36750911
2021 Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis. Cell communication and signaling : CCS 25 33627137
2009 Neither MafA/L-Maf nor MafB is essential for lens development in mice. Genes to cells : devoted to molecular & cellular mechanisms 25 19624757
2001 Maf and Jun nuclear oncoproteins share downstream target genes for inducing cell transformation. The Journal of biological chemistry 25 11461901
2019 IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection. Scientific reports 23 30899058
2018 SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes. The Journal of clinical investigation 23 30059018
2017 Differentiation of IL-17-Producing Invariant Natural Killer T Cells Requires Expression of the Transcription Factor c-Maf. Frontiers in immunology 23 29163480
2015 Multiple functions of Maf in the regulation of cellular development and differentiation. Diabetes/metabolism research and reviews 23 26122665