Affinage

MAF

Transcription factor Maf · UniProt O75444

Length
373 aa
Mass
38.5 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAF (c-Maf) is a basic region/leucine zipper transcription factor that binds Maf recognition elements (MAREs) to control cell-type-specific gene programs across the immune system, lens, neural, vascular, and myeloid lineages (PMID:8674125, PMID:10383433). Maf-specific DNA recognition is structurally encoded by conserved basic-region residues (Arg57, Asn61) that read the extended GC sequences flanking the MARE core (PMID:19797082), and MAF can act as a homodimer or heterodimerize with Fos and Jun at AP-1/CRE-related sites (PMID:8108109). In the immune system MAF is the IL-4-specific transactivator that initiates Th2 cytokine production in synergy with NF-ATp (PMID:8674125, PMID:10403649), and it directly drives IL-10 and IL-21 programs to enforce regulatory and follicular helper phenotypes: it induces intestinal RORγt+ Treg and IL-10-producing commensal-specific Th17 cells that constrain colitogenic responses (PMID:29414937, PMID:38039966, PMID:30778241), cooperates with Sox5 to activate the RORγt promoter for Th17 differentiation (PMID:25073789), and serves as a Bcl6-independent switch factor for TFH versus TH17 fate in TGF-β-rich settings (PMID:38427718). MAF specifies γδ17 and ILC3/ILC2 effector identity by remodeling chromatin at Rorc while antagonizing the opposing TCF1/T-bet fate (PMID:30538336, PMID:31570496). Beyond immunity, MAF directs lens fiber cell differentiation by binding T-MARE sites in crystallin promoters (PMID:10383433, PMID:10603348, PMID:16675956), controls macrophage identity, M2/perivascular polarization, and metabolic programming via direct CSF1R regulation (PMID:19539733, PMID:31945018, PMID:34597123), specifies mechanoreceptor and dorsal-horn interneuron development (PMID:22345400, PMID:22514301), acts downstream of Neuregulin1 to drive Schwann-cell cholesterol biosynthesis for myelination (PMID:29748249), and sets hepatic sinusoidal endothelial and epidermal progenitor identity (PMID:35364013, PMID:25805135). As a myeloma oncogene, MAF transforming activity requires MARE-dependent transactivation (PMID:11461901, PMID:16247450), and its abundance is governed by a phosphodegron axis: GSK-3 phosphorylation triggers ubiquitination and proteasomal degradation (PMID:18042454), opposed by the deubiquitinases USP5, USP7, and Otub1 (PMID:28933784, PMID:31822558, PMID:32842143) and promoted by the E2 enzyme UBE2O (PMID:28673317); SUMOylation at K33 selectively attenuates IL-4 (but not IL-21) transactivation by altering promoter recruitment and coactivator engagement (PMID:20127678, PMID:30059018). A dominant human MAF mutation causes reduced high-frequency vibration sensitivity, linking MAF to mechanosensory function (PMID:22345400).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Established the biochemical basis of MAF as a bZIP factor capable of dimerizing with AP-1 family proteins, defining its DNA-binding modality.

    Evidence In vitro binding/co-IP with purified polypeptides and leucine-zipper/basic-region mutagenesis

    PMID:8108109

    Open questions at the time
    • Did not address in vivo target genes
    • Cellular function not assigned
  2. 1996 High

    Identified the first direct MAF target and function: it answered how Th2 cells transcriptionally activate IL-4, establishing MAF as a MARE-binding transactivator acting with NF-ATp.

    Evidence Footprinting, reporter transactivation, ectopic expression in Th1/B cells

    PMID:8674125

    Open questions at the time
    • Specificity among Th2 cytokines not yet defined
    • In vivo requirement not tested
  3. 1999 High

    Genetic loss-of-function resolved whether MAF is specifically required for IL-4 in vivo and revealed a parallel essential role in lens fiber differentiation, defining its tissue breadth.

    Evidence c-maf-null mice with cytokine readouts; lens histology and crystallin promoter binding/reporter assays

    PMID:10383433 PMID:10403649 PMID:10603348

    Open questions at the time
    • Mechanism of crystallin locus activation not detailed
    • How IL-4 specificity versus IL-13 is enforced unresolved
  4. 2006 Medium

    Defined how MAF transforms cells, showing transformation requires MARE-dependent transactivation rather than obligate heterodimerization, and identified shared MAF/Jun target genes.

    Evidence Chicken embryo fibroblast transformation with domain-swap and dominant-negative Jun constructs; T-cell transgenic lymphoma model

    PMID:11461901 PMID:16247450 PMID:16424013

    Open questions at the time
    • Direct oncogenic target genes in human myeloma not yet mapped
    • Single-lab transformation assays
  5. 2009 High

    Provided the structural mechanism for MARE recognition, explaining how Maf-family basic-region residues read extended flanking GC sequences distinct from other bZIP factors.

    Evidence X-ray crystallography of MafG-DNA complex with functional residue validation

    PMID:19797082

    Open questions at the time
    • Structure solved for MafG, not c-Maf directly
    • Heterodimer DNA complexes not crystallized
  6. 2009 High

    Extended MAF's transcriptional repertoire to IL-10 and macrophage identity, broadening it from a Th2-specific factor to a multilineage regulator.

    Evidence Retroviral transduction with promoter MARE reporters (IL-10); knockout plus EMSA/reporter (F4/80); double-knockout with shRNA epistasis (macrophage self-renewal)

    PMID:19414776 PMID:19539733 PMID:19892988

    Open questions at the time
    • Direct genome-wide targets not yet defined
    • Relationship between repressive and activating modes unclear
  7. 2012 High

    Established MAF's role in nervous-system development and human sensory function, linking it to mechanoreceptor and interneuron differentiation and a dominant human vibration-sensitivity phenotype.

    Evidence Constitutive and conditional knockout mice with electrophysiology and IHC; human dominant MAF mutation analysis

    PMID:22345400 PMID:22514301

    Open questions at the time
    • Direct neuronal target genes not identified
    • Molecular basis of the dominant human allele not dissected
  8. 2014 High

    Identified MAF cofactors and a key post-translational stabilizer, showing Sox5 cooperation for Th17 fate and USP5 deubiquitination controlling MAF abundance.

    Evidence Domain-mapped physical interaction with Sox5 plus epistasis; co-IP, ubiquitination assays, and site-directed mutagenesis (K308/K347) for USP5; systematic lysine mutagenesis of degradation sites

    PMID:25073789 PMID:25448412 PMID:28933784

    Open questions at the time
    • Full E3 ligase responsible for K48 chains not fully defined
    • Lysosomal versus proteasomal balance unresolved
  9. 2018 High

    Defined MAF as a master regulator of regulatory and effector lymphocyte programs and dissected SUMOylation as a switch tuning IL-4 versus IL-21 output.

    Evidence Conditional knockouts across Treg, γδ17, and disease contexts with ATAC-seq/genomic footprinting; K33 SUMO-site mutagenesis with ChIP and transgenic mice

    PMID:20127678 PMID:29127150 PMID:29414937 PMID:29662170 PMID:30059018 PMID:30538336

    Open questions at the time
    • How a single factor selects opposing programs context-dependently is incompletely mapped
    • Coactivator/corepressor switching at additional loci not characterized
  10. 2019 High

    Expanded MAF's deubiquitinase network (Otub1, USP7) and its oncogenic stabilization, while defining intestinal Treg metabolic control and Tph helper function.

    Evidence MS, co-IP, ubiquitination and domain mutagenesis, xenografts (DUBs); germ-free transfer epistasis (intestinal Treg); CRISPR deletion in human Tph cells

    PMID:30778241 PMID:31536480 PMID:31570496 PMID:31822558 PMID:32842143

    Open questions at the time
    • Relative contributions of USP5/USP7/Otub1 in vivo unresolved
    • Direct ILC3 target genes beyond Rorc/T-bet not fully mapped
  11. 2020 High

    Defined MAF as a metabolic and identity checkpoint in tissue macrophages and endothelium, including direct CSF1R regulation and immunosuppressive polarization in cancer.

    Evidence Myeloid- and endothelium-restricted knockouts with ChIP, metabolomics, scRNA-seq, and tumor models

    PMID:31945018 PMID:34597123 PMID:35364013

    Open questions at the time
    • Upstream signals inducing MAF in each niche differ and are not unified
    • Direct metabolic-gene targets only partially mapped
  12. 2024 High

    Resolved MAF as the Bcl6-independent TFH/TH17 switch factor in TGF-β environments, clarifying its decision-making logic in helper T cell fate.

    Evidence In vitro TFH differentiation and in vivo immunization with Bcl6 and c-Maf conditional knockouts

    PMID:38427718

    Open questions at the time
    • Genome-wide CXCR5/TFH targets of MAF not detailed
    • Interplay with SUMO/DUB regulation in this context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single MARE-binding factor is wired to select among opposing transcriptional programs (e.g., activation vs repression, IL-4 vs IL-21, RORγt vs T-bet) in a cell-type-specific manner remains the central open question.
  • No unified model of context-dependent cofactor/PTM selection
  • Genome-wide direct target maps incomplete across most lineages

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-1266738 Developmental Biology 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3
Partners
BCL6FOSJUNMYBOTUB1SOX5USP5USP7

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 c-Maf, a basic region/leucine zipper transcription factor, directly binds a c-Maf response element (MARE) in the proximal IL-4 promoter and transactivates IL-4 expression in Th2 cells; it acts in synergy with NF-ATp to initiate endogenous IL-4 production. DNA binding assays (footprinting), reporter gene transactivation assays, ectopic expression in Th1 cells and B cells Cell High 8674125
1999 c-Maf is selectively required for IL-4 gene transcription in vivo; c-maf-/- CD4+ and NK T cells are markedly deficient in IL-4 production but produce normal levels of IL-13 and IgE, establishing that c-Maf's function is specific to IL-4 among Th2 cytokines. Gene knockout (c-maf-/- mice), cytokine measurement by ELISA and intracellular staining Immunity High 10403649
1999 c-Maf is required for differentiation of lens fiber cells and crystallin gene expression; c-maf-null mice lack normal lenses due to defective fiber cell differentiation, and c-Maf transactivates crystallin gene promoters. Gene targeting/knockout (c-maf-null mice), histology, lacZ reporter for expression visualization, crystallin gene expression analysis The Journal of biological chemistry High 10383433
1999 c-Maf is required for posterior lens fiber cell elongation and crystallin gene expression in vivo; c-Maf protein binds to T-MARE sites in αA-, βB2-, and βA4-crystallin promoters, and a point mutation in the αA-crystallin promoter that abolishes promoter function also abolishes c-Maf binding. Gene targeting (Maf(lacZ) knock-in mice), recombinant protein binding to crystallin promoter T-MARE sites, reporter gene assays Development (Cambridge, England) High 10603348
1994 c-Maf (and Nrl) bind specifically to AP-1 and CRE sites and form heterodimers with Fos and Jun in vitro; mutations in the leucine zipper or basic region inhibit heterodimer formation and DNA binding. In vitro binding assays with purified polypeptides, co-immunoprecipitation with antisera against each subunit, leucine zipper/basic region mutagenesis Oncogene High 8108109
2007 GSK-3 phosphorylates Maf proteins (demonstrated sequentially on MafA residues S49, T53, T57, S61), triggering ubiquitination and proteasomal degradation; paradoxically, this phosphorylation also increases transcriptional activity through recruitment of the co-activator P/CAF, which in turn protects MafA from degradation. Microarray analysis, phosphorylation site mapping by mutagenesis, ubiquitination assays, co-activator (P/CAF) co-immunoprecipitation, reporter gene assays Molecular cell High 18042454
2009 c-Maf directly regulates IL-10 expression during Th17 polarization by binding to a MARE motif in the IL-10 promoter; retroviral transduction of c-Maf induces IL-10 in Stat6-deficient CD4 and CD8 T cells. Retroviral transduction, reporter gene assay with IL-10 promoter MARE, gene array analysis Journal of immunology Medium 19414776
2009 c-Maf is required for F4/80 expression in macrophages in vivo; c-Maf directly binds to a half-MARE site in the F4/80 promoter to activate transcription, as shown by luciferase reporter assays and EMSA. c-Maf knockout mice (null mutant phenotype), luciferase reporter assay, EMSA Gene Medium 19539733
2009 Combined MafB and c-Maf deficiency enables self-renewal of mature macrophages without loss of differentiated phenotype; this requires concomitant up-regulation of KLF4 and c-Myc, as shown by shRNA inactivation. Gene knockout (MafB/c-Maf double-deficient cells), shRNA knockdown of KLF4 and c-Myc, transplantation assay Science High 19892988
2009 Crystal structure of MafG-DNA complex reveals that two conserved residues Arg57 and Asn61 in the basic region mediate Maf-specific recognition of the extended GC sequences flanking the MARE core, an alternative DNA recognition mechanism relative to other bZIP factors. X-ray crystallography of MafG-DNA complex Molecular and cellular biology High 19797082
1998 c-Maf physically associates with c-Myb to form inhibitory complexes that repress c-Myb-dependent CD13/APN transcription in myeloid cells in a developmentally regulated manner; complex levels peak at the promyelocyte stage. Reporter gene assays, physical interaction (co-immunoprecipitation), developmental stage analysis of complex levels Molecular and cellular biology Medium 9566892
1999 c-Maf overexpression in bipotent myeloid progenitors drives monocytic differentiation followed by apoptosis, linked to c-Maf/c-Myb complex formation inhibiting c-Myb targets including Bcl-2 and CD13/APN. Inducible c-Maf overexpression in myeloid progenitor cell lines, flow cytometric lineage analysis, complex formation assays Blood Medium 10477683
2002 c-Maf negatively regulates ARE-mediated detoxifying enzyme gene expression (NQO1, GST Ya) by binding to the ARE as homodimers and heterodimers with small Maf proteins, but not as heterodimers with Nrf2; the transcriptional activation domain of c-Maf is not required for this repression. Reporter gene assays, EMSA (band and supershift assays), in vitro translated protein binding, mutational analysis of ARE, deletion constructs Oncogene High 12149651
2012 c-Maf is essential for development and function of several rapidly adapting mechanoreceptor types in mice; Pacinian corpuscles are severely atrophied in c-Maf mutant mice, and humans carrying a dominant MAF mutation show reduced sensitivity to high-frequency vibration. c-Maf knockout mice (phenotypic analysis of mechanoreceptors), human genetic mutation analysis, electrophysiological measurements Science High 22345400
2012 c-Maf is required for development of dorsal horn laminae III/IV interneurons and for differentiation of MafA+/Ret+/GFRα2+ low-threshold mechanoreceptors in DRG, as well as for proper central and peripheral projections of mechanoreceptive DRG neurons. c-Maf conditional knockout mice, immunohistochemistry, marker gene expression analysis The Journal of neuroscience Medium 22514301
2012 Bcl6 and c-Maf (Maf) cooperate in human Tfh cell differentiation: Maf introduction induces IL-21 expression and CXCR5, while co-expression of Bcl6 and Maf cooperatively induces CXCR4, PD-1, and ICOS. Retroviral introduction of Bcl6 and/or Maf into primary human CD4 T cells, flow cytometry, gene expression analysis Journal of immunology Medium 22427637
2014 Sox5 physically associates with c-Maf via the HMG domain of Sox5 and the DNA-binding domain of c-Maf; Sox5 and c-Maf together directly activate the RORγt promoter in CD4+ T cells and cooperatively induce Th17 cell differentiation downstream of Stat3 and upstream of RORγt. Retrovirus-mediated co-expression in Stat3-deficient and RORγt-deficient CD4+ T cells (epistasis), physical interaction mapping, promoter reporter assay The Journal of experimental medicine High 25073789
2017 USP5 (deubiquitinase) interacts with c-Maf and prevents its proteasomal degradation by decreasing K48-linked polyubiquitination; the cryptic ZnF domain and C-box domain of USP5 interact with c-Maf, while the UBA1/UBA2 domain partly increases c-Maf stability; lysines K308 and K347 of c-Maf are critical for USP5-mediated deubiquitination. Co-immunoprecipitation, ubiquitination assays, domain deletion/mapping, site-directed mutagenesis (K308R, K347R), shRNA knockdown, luciferase assay Cell death & disease High 28933784
2017 UBE2O (ubiquitin-conjugating enzyme) interacts with c-Maf and mediates its K48-linked polyubiquitination and subsequent proteasomal degradation, reducing c-Maf transcriptional activity and cyclin D2 expression in myeloma cells. Mass spectrometry, co-immunoprecipitation, ubiquitination assays, luciferase transcriptional activity assay, shRNA/overexpression in myeloma cell lines and xenografts Journal of hematology & oncology Medium 28673317
2018 c-MAF transcription factor is required for induction of RORγt+FOXP3+ regulatory T cells in the large intestine in response to Helicobacter hepaticus; c-MAF-deficient Treg cells fail to differentiate and produce IL-10, leading to expansion of colitogenic TH17 cells and spontaneous colitis. Conditional knockout of c-MAF in Treg compartment, colitis model, flow cytometry, cytokine measurement Nature High 29414937
2018 c-Maf is a negative regulator of IL-2 transcription in CD4+ T cells; bivariate genomic footprinting identified enhanced NFAT activity in c-Maf-deficient cells; reduced RORγt expression upon c-Maf deficiency is IL-2-dependent. T cell-specific c-Maf knockout mice, in vivo disease models (malaria, allergy, autoimmunity), bivariate genomic footprinting, cytokine and transcription factor expression analysis Nature immunology High 29662170
2018 c-Maf is an essential commitment factor for IL-17-producing γδ T cells (Tγδ17); Maf deficiency causes an absolute lineage block at the CD24+CD45RBlo γδ thymocyte stage; c-Maf promotes chromatin accessibility at Rorc and Blk while antagonizing TCF1 to prevent IFN-γ-producing γδ T cell fate. Conditional c-Maf knockout mice, ATAC-seq (chromatin accessibility), transcriptomics, flow cytometry Nature immunology High 30538336
2018 SUMOylation of c-Maf at lysine-33 attenuates its IL-4 transcriptional activity by reducing its recruitment to the Il4 promoter without altering subcellular localization or protein stability; c-Maf interacts with Ubc9 and PIAS1 (SUMO pathway enzymes). Yeast two-hybrid (interaction with Ubc9/PIAS1), in vitro and in vivo SUMOylation assays, site-directed mutagenesis (K33R), chromatin immunoprecipitation, retroviral transduction in c-Maf-deficient Th2 cells European journal of immunology High 20127678
2018 SUMO-defective c-Maf (K→R mutation at SUMOylation site) preferentially transactivates Il21 over Il4 by selectively inhibiting recruitment of Daxx/HDAC2 to the Il21 promoter and enhancing CBP/p300-mediated histone acetylation at that locus. Transgenic NOD mice (wild-type vs. SUMOylation-mutant c-Maf), promoter ChIP assays, pharmacological CBP/p300 inhibition The Journal of clinical investigation High 30059018
2019 Otub1 (OTU deubiquitinase) interacts with c-Maf (identified by mass spectrometry), abrogates K48-linked polyubiquitination of c-Maf and prevents its degradation, enhancing its transcriptional activity; this activity requires Otub1 Lys71 and its N-terminus but is independent of UBE2O. Mass spectrometry identification, co-immunoprecipitation, ubiquitination assays, domain mutagenesis (Lys71), luciferase assay, shRNA knockdown, xenograft models Blood High 32842143
2019 USP7 (deubiquitinase) interacts with c-Maf, MafA, and MafB and blocks their polyubiquitination and proteasomal degradation, thereby promoting Maf transcriptional activity and myeloma cell survival. Mass spectrometry (MafB interactome), co-immunoprecipitation, ubiquitination assays, luciferase assay, shRNA knockdown, pharmacological inhibition (P5091) The Journal of biological chemistry Medium 31822558
2014 c-MAF ubiquitination is mediated by multiple lysine residues; no single lysine alone is sufficient, but K85 and K350 together are sufficient (though not the only pair); c-MAF is also degraded by lysosomes in addition to proteasomes. Systematic lysine-to-arginine mutagenesis, cell-based ubiquitination assays, luciferase reporter assay for transcriptional activity, lysosomal inhibitor treatment The international journal of biochemistry & cell biology Medium 25448412
2016 MAF overexpression (as in t(14;16) multiple myeloma) confers innate resistance to proteasome inhibitors (bortezomib, carfilzomib) by stabilizing MAF protein; proteasome inhibitor exposure blocks GSK3β-mediated MAF degradation, increasing MAF protein stability. Cell line models with t(14;16) translocation, loss-of-function (MAF silencing) and gain-of-function (MAF overexpression), PI sensitivity assays, apoptosis/caspase assays Blood Medium 27793878
2006 c-Maf's cell-transforming activity requires transactivation through MARE (replacement of transactivation domain with VP16 enhances transformation; fusion with transcriptional repressor abolishes it); c-Maf and Jun share downstream target genes for transformation; heterodimer formation with other bZIP factors is not required for Maf-induced transformation. Chicken embryo fibroblast transformation assay, domain swap/fusion constructs (VP16 activation domain, Mxi1 repressor domain, GCN4 leucine zipper), dominant-negative Jun Oncogene Medium 16247450
2006 c-Maf overexpression in T cells drives T-cell lymphoma in transgenic mice, with upregulation of cyclin D2, integrin β7, and ARK5 as downstream target genes. T-cell-specific c-Maf transgenic mice, gene expression analysis of lymphoma cells Cancer research Medium 16424013
2018 c-Maf is required for Treg specialization: it is essential for generation of RORγt+ Tregs and T follicular regulatory cells in mice, but not for adipose-resident Tregs; c-Maf is induced in Tregs by IL-6 and TGF-β. Conditional c-Maf knockout in Tregs, flow cytometric analysis of Treg subsets, cytokine stimulation experiments Journal of immunology Medium 29127150
2019 c-Maf-dependent intestinal Treg cells constrain microbiota-dependent TH17 and IgA responses; c-Maf deficiency in Tregs leads to dysbiosis sufficient to induce exacerbated intestinal TH17 responses upon germ-free transfer; c-Maf controls IL-10 production and prevents excessive PI3K/Akt/mTORC1 signaling in intestinal Tregs. Conditional c-Maf knockout in Treg compartment, germ-free mouse transfer experiments, cytokine and signaling pathway analysis Nature immunology High 30778241
2020 c-Maf is a critical controller of immunosuppressive (M2-like) macrophage polarization in cancer; it has direct binding sites within a conserved noncoding sequence of the Csf-1r gene; c-Maf also acts as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis; myeloid-specific deletion reduces tumor burden with enhanced T cell immunity. Myeloid-specific c-Maf knockout mice, ChIP (Csf-1r binding sites), metabolomics, tumor models, T cell functional assays The Journal of clinical investigation High 31945018
2020 c-Maf enforces ILC3 identity by promoting RORγt activity and type 3 effector gene expression while directly restraining T-bet expression; c-Maf and T-bet form a negative feedback loop in CCR6- ILC3s. c-Maf conditional knockout, transcriptomics, ATAC-seq (chromatin accessibility and TF motif enrichment), flow cytometry The Journal of experimental medicine High 31570496
2021 MAF directly activates β/γ-crystallin gene promoters and activates TGF-β1-Smad signaling to upregulate crystallins in high myopia lenses; mechanistic studies identify a MAF-TGF-β1-crystallin axis. Mechanistic studies in myopia mouse models and human high myopic lenses, promoter activation assays, Smad signaling analysis Nature communications Medium 33833231
2021 c-Maf is a critical perinatal transcriptional switch for hepatic sinusoidal endothelial cell identity; endothelium-restricted c-Maf deletion disrupts liver sinusoidal development, expands postnatal hematopoiesis, and increases pro-fibrotic sensitivity; enforced c-Maf expression in generic human endothelial cells activates a liver sinusoidal transcriptional program. Endothelium-restricted c-Maf knockout mice, scRNA-seq, enforced c-Maf overexpression in human endothelial cells, functional hepatocyte co-culture assays Cell stem cell High 35364013
2021 c-MAF-dependent perivascular macrophages in white adipose tissue regulate metabolic syndrome; conditional c-MAF deletion in macrophage lineages ablates perivascular macrophages and alters muscularis macrophage program, with macrophage-specific c-MAF deletion improving metabolic parameters under high-fat diet. Macrophage lineage-specific c-MAF conditional knockout, single-cell RNA-seq, metabolic phenotyping (glucose tolerance, weight, adipose inflammation) Science immunology High 34597123
2022 c-Maf is required for optimal type 2 cytokine production and memory-like (trained) responses in group-2 innate lymphoid cells (ILC2s); c-Maf is induced by IL-33/IL-25 and allergen (papain) exposure; c-Maf-deficient mouse and human ILC2s fail to show trained immunity upon repeated challenge. c-Maf deletion in ILCs (mouse), transcriptomic analysis, knockdown in human ILC2s, repeated allergen challenge model The EMBO journal Medium 35467036
2024 TGF-β induces CXCR5 expression in mouse CD4+ T cells to drive TFH differentiation via c-Maf, but independently of Bcl6; c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-β-rich environments both in vitro and in vivo. In vitro TFH differentiation protocol, Bcl6 and c-Maf conditional knockouts, CXCR5 expression analysis, in vivo immunization experiments Science immunology High 38427718
2018 Maf acts downstream of Neuregulin1 (Nrg1) signaling in Schwann cells to directly bind enhancers of cholesterol synthesis genes, promoting cholesterol biosynthesis required for myelination; Nrg1-calmodulin-dependent kinases regulate Maf transcription, while Nrg1-MAPK signaling stabilizes Maf protein. Genetic ablation of Maf in Schwann cells, ChIP (Maf binding to cholesterol synthesis gene enhancers), epistasis with Nrg1 signaling, kinase inhibition experiments Genes & development High 29748249
2007 c-maf is required for AhR-dependent β7-integrin induction in macrophages by benzo(a)pyrene; c-Maf binds to a Maf-responsive element in the β7-integrin promoter (demonstrated by ChIP and EMSA), and c-maf knockdown impairs induction. shRNA knockdown of c-maf, chromatin immunoprecipitation (ChIP), EMSA, chemical inhibition of AhR Biochemical and biophysical research communications Medium 17490615
2010 IL-2 induces STAT5 binding to specific sites in the c-MAF promoter, thereby promoting c-MAF expression in human CD4 T cells; IL-2 and IL-6 synergistically induce c-MAF expression; blockade of IL-2 signaling (daclizumab or JAK3 inhibitor) reduces c-MAF and IL-4 expression. Chromatin immunoprecipitation (STAT5 binding to c-MAF promoter), cytokine stimulation experiments, pharmacological inhibition (daclizumab, R333), primary human CD4 T cells Journal of immunology Medium 21876034
2007 c-Maf interacts with c-Myb in CD4 T cells to reduce Bcl-2 expression and increase susceptibility to apoptosis; c-Maf/c-Myb complex formation is enhanced following TCR engagement and prevents c-Myb binding to the Bcl-2 promoter; Bcl-2 overexpression corrects the apoptosis defect. c-Maf transgenic mice, co-immunoprecipitation, chromatin immunoprecipitation (c-Myb at Bcl-2 promoter), reporter gene assay, Bcl-2 rescue transgene European journal of immunology Medium 17823980
2001 Maf's transforming activity requires transactivation through MARE; heterodimer formation with other bZIP factors is dispensable for transformation; Maf and Jun share downstream MARE-regulated target genes for cell transformation, as a Jun dominant-negative construct blocks both Jun- and Maf-induced transformation. Chicken embryo fibroblast transformation assays, domain swap constructs (VP16 activator, Mxi1 repressor, GCN4 leucine zipper), dominant-negative Jun constructs The Journal of biological chemistry Medium 11461901
2023 Intestinal commensal-specific Th17 cells acquire an anti-inflammatory, IL-10-producing phenotype driven by c-MAF; these cells suppress effector T cell activity in an IL-10-dependent and c-MAF-dependent manner in vitro and in vivo. Conditional c-MAF deletion in T cells, antigen-specific T cell tracking, in vitro and in vivo suppression assays, cytokine measurement Immunity High 38039966
2006 c-Maf regulates the alphaA-crystallin locus through binding to the promoter and distal control regions (DCR3), associated with broad histone H3K9-hyperacetylation and increased abundance of chromatin remodeling enzymes Brg1 and Snf2h at the locus. Chromatin immunoprecipitation (ChIP) for c-Maf, CREB, Pax6 binding, histone acetylation marks, and chromatin remodeling enzymes; reporter gene assays in lens explants The EMBO journal Medium 16675956
2019 CRISPR-mediated deletion of MAF abrogates the ability of PD-1hiCXCR5- T peripheral helper (Tph) cells to induce memory B cell differentiation into plasmablasts in vitro. CRISPR-Cas9 deletion of MAF in human Tph cells, B cell differentiation co-culture assay JCI insight Medium 31536480
2015 MAF and MAFB are necessary and sufficient for epidermal progenitor differentiation; MAF:MAFB regulate 393 genes including downstream transcription factors GRHL3, ZNF750, KLF4, and PRDM1; ChIP-seq confirms MAF:MAFB binding to these TF gene loci. ChIP-seq (MAF:MAFB binding genome-wide), siRNA knockdown and overexpression, kinetic transcriptome analysis, organotypic epidermal regeneration Developmental cell High 25805135

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 The proto-oncogene c-maf is responsible for tissue-specific expression of interleukin-4. Cell 541 8674125
2018 c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 426 29414937
2002 Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors. Gene 393 12234662
1999 The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 318 10403649
2012 Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 300 22427637
2019 PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. JCI insight 249 31536480
2009 MafB/c-Maf deficiency enables self-renewal of differentiated functional macrophages. Science (New York, N.Y.) 237 19892988
1997 The world according to Maf. Nucleic acids research 237 9224592
1999 Regulation of lens fiber cell differentiation by transcription factor c-Maf. The Journal of biological chemistry 215 10383433
2000 Regulation of mouse lens fiber cell development and differentiation by the Maf gene. Development (Cambridge, England) 205 10603348
2009 c-Maf regulates IL-10 expression during Th17 polarization. Journal of immunology (Baltimore, Md. : 1950) 200 19414776
1999 Requirement for the c-Maf transcription factor in crystallin gene regulation and lens development. Proceedings of the National Academy of Sciences of the United States of America 200 10097114
2016 Small Maf proteins (MafF, MafG, MafK): History, structure and function. Gene 199 27058431
1994 Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun. Oncogene 172 8108109
2015 A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation. Developmental cell 162 25805135
2019 c-Maf-dependent Treg cell control of intestinal TH17 cells and IgA establishes host-microbiota homeostasis. Nature immunology 154 30778241
2020 Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer. The Journal of clinical investigation 148 31945018
2012 The transcription factor c-Maf controls touch receptor development and function. Science (New York, N.Y.) 142 22345400
2007 Small Maf proteins in mammalian gene control: mere dimerization partners or dynamic transcriptional regulators? Journal of molecular biology 131 18201722
2012 The small MAF transcription factors MAFF, MAFG and MAFK: current knowledge and perspectives. Biochimica et biophysica acta 127 22721719
2018 c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells. Nature immunology 124 29662170
2014 Sox5 and c-Maf cooperatively induce Th17 cell differentiation via RORγt induction as downstream targets of Stat3. The Journal of experimental medicine 109 25073789
2018 The transcription factor c-Maf is essential for the commitment of IL-17-producing γδ T cells. Nature immunology 106 30538336
1995 Activity and expression of murine small Maf family protein MafK. The Journal of biological chemistry 106 7706310
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
1997 Rat maf related genes: specific expression in chondrocytes, lens and spinal cord. Oncogene 88 9038383
2023 Intestinal microbiota-specific Th17 cells possess regulatory properties and suppress effector T cells via c-MAF and IL-10. Immunity 82 38039966
2018 An immunoregulatory and tissue-residency program modulated by c-MAF in human TH17 cells. Nature immunology 81 30201991
2020 CncC/Maf-mediated xenobiotic response pathway in insects. Archives of insect biochemistry and physiology 79 32281173
2017 Inhibition of the deubiquitinase USP5 leads to c-Maf protein degradation and myeloma cell apoptosis. Cell death & disease 75 28933784
1998 c-Maf interacts with c-Myb to regulate transcription of an early myeloid gene during differentiation. Molecular and cellular biology 72 9566892
2007 Multiple mechanisms and functions of maf transcription factors in the regulation of tissue-specific genes. Journal of biochemistry 71 17569705
2017 The Transcription Factor c-Maf Promotes the Differentiation of Follicular Helper T Cells. Frontiers in immunology 69 28496444
2002 c-Maf negatively regulates ARE-mediated detoxifying enzyme genes expression and anti-oxidant induction. Oncogene 69 12149651
1999 c-Maf induces monocytic differentiation and apoptosis in bipotent myeloid progenitors. Blood 69 10477683
2021 Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia. Nature communications 68 33833231
2009 Structural basis of alternative DNA recognition by Maf transcription factors. Molecular and cellular biology 68 19797082
2006 Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human. Cancer research 66 16424013
2020 c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program. The Journal of experimental medicine 65 31570496
2020 Xenobiotic transcription factors CncC and maf regulate expression of CYP321A16 and CYP332A1 that mediate chlorpyrifos resistance in Spodoptera exigua. Journal of hazardous materials 62 32512455
2018 Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects. Human mutation 61 29314435
2016 MAF protein mediates innate resistance to proteasome inhibition therapy in multiple myeloma. Blood 61 27793878
2022 Specification of fetal liver endothelial progenitors to functional zonated adult sinusoids requires c-Maf induction. Cell stem cell 59 35364013
2020 Malat1 Suppresses Immunity to Infection through Promoting Expression of Maf and IL-10 in Th Cells. Journal of immunology (Baltimore, Md. : 1950) 58 32321759
2017 Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt RORγt+ and Follicular Phenotypes. Journal of immunology (Baltimore, Md. : 1950) 56 29127150
2020 c-MAF, a Swiss Army Knife for Tolerance in Lymphocytes. Frontiers in immunology 55 32117317
2021 c-MAF-dependent perivascular macrophages regulate diet-induced metabolic syndrome. Science immunology 52 34597123
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
2019 Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function. Cell reports 49 30699346
2006 Cell context reveals a dual role for Maf in oncogenesis. Oncogene 48 16247450
1997 Differential expression of maf-1 and maf-2 genes in the developing rat lens. Investigative ophthalmology & visual science 47 9375588
2021 Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF. The Journal of clinical investigation 44 34403373
2015 Regulation of c-Maf and αA-Crystallin in Ocular Lens by Fibroblast Growth Factor Signaling. The Journal of biological chemistry 44 26719333
2022 The IL-21-TET2-AIM2-c-MAF pathway drives the T follicular helper cell response in lupus-like disease. Clinical and translational medicine 43 35343082
2019 The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival. The Journal of biological chemistry 43 31822558
2017 The ubiquitin-conjugating enzyme UBE2O modulates c-Maf stability and induces myeloma cell apoptosis. Journal of hematology & oncology 42 28673317
2005 Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1-deficient mice. Blood 41 15845902
2007 c-Maf expression in angioimmunoblastic T-cell lymphoma. The American journal of surgical pathology 40 18059226
2019 Mebendazole elicits potent antimyeloma activity by inhibiting the USP5/c-Maf axis. Acta pharmacologica Sinica 38 31197245
2019 A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation. Immunity 38 31422869
2006 Carcinogenesis and transcriptional regulation through Maf recognition elements. Cancer science 37 17129360
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
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
2022 Molecular Mechanisms Driving IL-10- Producing B Cells Functions: STAT3 and c-MAF as Underestimated Central Key Regulators? Frontiers in immunology 33 35359922
2014 MAF mediates crosstalk between Ras-MAPK and mTOR signaling in NF1. Oncogene 33 24509877
2020 c-Maf restrains T-bet-driven programming of CCR6-negative group 3 innate lymphoid cells. eLife 32 32039762
2016 Differential expression patterns of MafB and c-Maf in macrophages in vivo and in vitro. Biochemical and biophysical research communications 31 26996125
1998 Rat maf-related factors: the specificities of DNA binding and heterodimer formation. Biochemical and biophysical research communications 31 9571165
2020 Maf and Mafb control mouse pallial interneuron fate and maturation through neuropsychiatric disease gene regulation. eLife 30 32452758
2020 MAFB and MAF Transcription Factors as Macrophage Checkpoints for COVID-19 Severity. Frontiers in immunology 29 33312178
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
2009 c-Maf is essential for the F4/80 expression in macrophages in vivo. Gene 29 19539733
2018 Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells. Genes & development 28 29748249
2017 Small Maf functions in the maintenance of germline stem cells in the Drosophila testis. Redox biology 28 29245136
2011 IL-2 regulates expression of C-MAF in human CD4 T cells. Journal of immunology (Baltimore, Md. : 1950) 28 21876034
2007 AhR- and c-maf-dependent induction of beta7-integrin expression in human macrophages in response to environmental polycyclic aromatic hydrocarbons. Biochemical and biophysical research communications 28 17490615
2024 TGF-β specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf. Science immunology 27 38427718
2022 A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4+ T cells and is defective in Crohn´s disease patients. Mucosal immunology 27 35169232
2012 The tumor suppressor p53 regulates c-Maf and Prox-1 to control lens differentiation. Current molecular medicine 27 22827438
2022 c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells. The EMBO journal 26 35467036
2002 c-Maf, the gammaD-crystallin Maf-responsive element and growth factor regulation. Nucleic acids research 26 11842109
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
2007 c-Maf interacts with c-Myb to down-regulate Bcl-2 expression and increase apoptosis in peripheral CD4 cells. European journal of immunology 25 17823980
2001 Maf and Jun nuclear oncoproteins share downstream target genes for inducing cell transformation. The Journal of biological chemistry 25 11461901
2018 SUMO-defective c-Maf preferentially transactivates Il21 to exacerbate autoimmune diabetes. The Journal of clinical investigation 24 30059018
2015 Multiple functions of Maf in the regulation of cellular development and differentiation. Diabetes/metabolism research and reviews 24 26122665
2003 Mitogen-activated protein kinase pathway mediates DBP-maf-induced apoptosis in RAW 264.7 macrophages. Journal of cellular biochemistry 24 12938159
2019 IL-27 promotes NK cell effector functions via Maf-Nrf2 pathway during influenza infection. Scientific reports 23 30899058
2004 c-maf in multiple myeloma: an oncogene enhancing tumor-stroma interactions. Cancer cell 23 14998484
2023 Cancer stem cell-derived CHI3L1 activates the MAF/CTLA4 signaling pathway to promote immune escape in triple-negative breast cancer. Journal of translational medicine 21 37838657
2003 Regulation and differential expression of the c-maf gene in differentiating cultured cells. Biochemical and biophysical research communications 21 14521912
2021 Functional analysis of large MAF transcription factors and elucidation of their relationships with human diseases. Experimental animals 20 33762508
2014 KLF13 cooperates with c-Maf to regulate IL-4 expression in CD4+ T cells. Journal of immunology (Baltimore, Md. : 1950) 20 24821970
2001 Variable effects of transgenic c-Maf on autoimmune diabetes. Diabetes 20 11147792
2017 Prostaglandin E2 inhibits Tr1 cell differentiation through suppression of c-Maf. PloS one 19 28604806
2010 SUMOylation attenuates c-Maf-dependent IL-4 expression. European journal of immunology 19 20127678

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