Affinage

MAFF

Transcription factor MafF · UniProt Q9ULX9

Length
164 aa
Mass
17.8 kDa
Annotated
2026-06-10
43 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAFF is a small nuclear bZIP transcription factor that lacks an intrinsic transactivation domain and functions as a context-dependent transcriptional switch coordinating inflammatory, metabolic, and cell-fate programs (PMID:8361754, PMID:27058431). It dimerizes through its leucine zipper: homodimers are transcriptionally inert or repressive, whereas obligatory heterodimers with CNC-family proteins (Nrf1, Nrf2, NF-E2) and Bach-family proteins (Bach1, Bach2)—which cannot bind DNA alone—activate or repress target genes at MAF recognition elements depending on partner and cellular context (PMID:12490281, PMID:27058431). Through BACH1 heterodimers, MAFF directly binds promoters to repress LDLR under inflammation (PMID:33626882) and to activate IL11 and CLCF1, both feeding STAT3 signaling in cancer and liver injury (PMID:34262028, PMID:40169936), while NRF2 partnership drives contraction-associated genes PTGS2 and OXTR in myometrium (PMID:41854048). MAFF directly controls a broad transcriptional program governing ferroptosis and lipid/iron metabolism—repressing SLC7A11 and activating SLC11A2, NCOA4, and AKR1C1 while reprogramming lipid metabolism enzymes (PMID:38266355, PMID:42209456, PMID:41206944)—and cell-cycle and death pathways via CDK6/CDKN2C, GATA4-MLKL necroptosis, and DUSP5-mediated ERK suppression (PMID:39151323, PMID:38266355, PMID:42153582). MAFF expression and stability are heavily regulated: it is rapidly and transcriptionally induced by IL-1β/TNF through NF-κB (PMID:16371591, PMID:33980595), its mRNA is exported and stabilized by the m6A reader YTHDC1 (PMID:40054588), and its protein is stabilized by BAP1-mediated removal of K48-linked ubiquitin and suppressed by HDAC6-mediated deacetylation (PMID:39151323, PMID:39412062). Loss-of-function in mice shows MAFF is dispensable for development (PMID:10409670).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1993 Medium

    Established MAFF as a small bZIP protein lacking the acidic transactivation domain of large Mafs, raising the question of how it could regulate transcription at all.

    Evidence Retroviral overexpression in CEF cells with soft-agar assay and structural analysis of cDNA, nuclear localization by immunostaining

    PMID:8361754

    Open questions at the time
    • No DNA target or dimerization partner identified
    • Weak transformation phenotype not mechanistically explained
  2. 1999 Medium

    Showed MAFF binds a defined promoter element (US-2 of the oxytocin receptor gene) and is enriched in term myometrium, giving the protein a concrete DNA-binding target.

    Evidence Yeast one-hybrid screening of myometrium cDNA library, EMSA, Northern hybridization

    PMID:10527846

    Open questions at the time
    • Did not establish whether binding required a heterodimeric partner
    • No functional transcriptional readout in cells
  3. 1999 High

    Genetic deletion in mice resolved whether MAFF is individually essential, showing it is dispensable for development while mapping its broad tissue expression via three promoters.

    Evidence MafF null mice with Mendelian analysis and lacZ knock-in reporter

    PMID:10409670

    Open questions at the time
    • Redundancy with MafG/MafK not directly tested here
    • No molecular target defined in vivo
  4. 2002 Medium

    Defined MAFF's dimerization logic, distinguishing it from other small Mafs: its homodimers are not repressive, while CNC heterodimers (Nrf1/Nrf2/NF-E2) act as weak activators.

    Evidence Reporter assays on globin/GCSl promoters with multiple dimerization partners across cell lines

    PMID:12490281

    Open questions at the time
    • Endogenous physiological targets not addressed
    • Context-dependence of activation vs repression not resolved
  5. 2002 Medium

    Linked MAFF expression to oxidative/electrophile stress, showing selective transcriptional induction by EpRE activators above other small Mafs.

    Evidence RT-PCR/Northern in HepG2 with actinomycin D transcription block

    PMID:11772409

    Open questions at the time
    • Did not show MAFF protein function downstream of induction
    • tBHQ failure left requirement for sMaf upregulation ambiguous
  6. 2005 Medium

    Identified inflammatory cytokines as a MAFF-specific induction signal, separating MAFF from MAFG/MAFK regulation.

    Evidence RT-PCR time-course and Western blot in myometrial cells with actinomycin D

    PMID:16371591

    Open questions at the time
    • Upstream transcription factor not yet identified
    • Downstream MAFF targets in this context not defined
  7. 2006 Medium

    Identified MIP as a coiled-coil interacting co-activator that confers transactivation onto an otherwise transactivation-deficient MAFF.

    Evidence Co-IP, in vitro binding, subcellular imaging, US2-reporter assay in HeLa; confirmed in a yeast reporter system in 2009

    PMID:16549056 PMID:19723544

    Open questions at the time
    • Physiological relevance of MIP co-activation outside reporter systems unclear
    • Endogenous target genes of the MAFF-MIP pair not mapped
  8. 2016 High

    Consolidated the obligatory-partner model: small Mafs including MAFF are indispensable DNA-binding partners for CNC and Bach proteins, acting as activators or repressors by context.

    Evidence Review synthesizing genetic, structural, and biochemical data across labs

    PMID:27058431

    Open questions at the time
    • Does not assign MAFF-specific endogenous targets
    • Partner-selection rules per cell type not specified
  9. 2019 Medium

    Provided the first direct endogenous target genes for MAFF, showing promoter occupancy and loss-of-function control of inflammatory cytokines CXCL1 and CSF3.

    Evidence siRNA knockdown, ChIP, RT-PCR, ELISA, paracrine co-culture

    PMID:30669188

    Open questions at the time
    • Heterodimeric partner at these promoters not identified
    • Single cell system
  10. 2021 High

    Identified BACH1 as a key MAFF heterodimer partner and showed context-switching: BACH1-MAFF represses LDLR under inflammation but activates IL11 to drive STAT3-dependent metastasis under hypoxia.

    Evidence ChIP-seq, ChIP-MS, RNA-seq, knockdown/overexpression, KO mice, patient correlation; metastasis model and invasion assays

    PMID:33626882 PMID:34262028

    Open questions at the time
    • What determines activator vs repressor outcome of BACH1-MAFF not mechanistically resolved
    • Cofactors distinguishing the two contexts unknown
  11. 2021 High

    Demonstrated MAFF acts as a host antiviral repressor of the HBV core promoter via competitive displacement of HNF-4α, and tied its induction to NF-κB downstream of IL-1β/TNF.

    Evidence siRNA screen with HBV reporter, CRISPR KO, ChIP, promoter mutagenesis, primary hepatocytes

    PMID:33980595

    Open questions at the time
    • Whether MAFF binds HBV promoter as homodimer or heterodimer not defined
    • Generality across HBV genotypes untested
  12. 2021 Medium

    Showed MAFF is itself a regulated target, with miR-320a directly suppressing MAFF mRNA to control beta-cell ROS, proliferation, and survival.

    Evidence RIP-Seq, luciferase, Western, AAV8 beta-cell delivery, islet transplantation, hyperglycemic clamp

    PMID:34631276

    Open questions at the time
    • Direct MAFF transcriptional targets in beta cells not mapped
    • Single lab
  13. 2024 High

    Established post-translational control of MAFF stability by BAP1 deubiquitination and linked stabilized MAFF to DUSP5-mediated ERK suppression in colorectal cancer.

    Evidence Quantitative proteomics, DUB library screen, Co-IP, ubiquitination assay, RNA-seq, xenografts

    PMID:39151323

    Open questions at the time
    • Identity of the E3 ligase adding K48 chains unknown
    • Whether DUSP5 is a direct MAFF target not shown
  14. 2024 High

    Defined MAFF as a direct dual regulator of ferroptosis and cell cycle (repressing SLC7A11, controlling CDK6/CDKN2C) acting downstream of cAMP/PKA/CREB1 in therapy-stressed lung adenocarcinoma.

    Evidence CRISPR screens, scRNA-seq, ChIP-seq, RNA-seq, xenografts

    PMID:38266355

    Open questions at the time
    • Heterodimeric partner at these promoters not defined
    • Balance between ferroptosis and cell-cycle effects per context unclear
  15. 2024 Medium

    Expanded MAFF's partner repertoire beyond CNC/Bach, showing BATF3 cooperation in repressing ZNF711 in ovarian cancer.

    Evidence Dual-luciferase, ChIP-PCR, Co-IP, immunofluorescence, siRNA, xenograft

    PMID:38908812

    Open questions at the time
    • Whether BATF3 binds DNA jointly with MAFF or modulates it indirectly unresolved
    • Single lab
  16. 2025 Medium

    Linked HDAC6-mediated deacetylation to suppression of MAFF function, with MAFF directly repressing KLF5 to limit fibrosis and inflammation in lupus nephritis.

    Evidence ChIP, dual luciferase, overexpression/knockdown, MRL/lpr mouse model

    PMID:39412062

    Open questions at the time
    • Acetylated MAFF residues not mapped
    • Direct vs indirect HDAC6 action on MAFF acetylation not fully resolved
  17. 2025 Medium

    Identified MAFF mRNA as an m6A/YTHDC1 client, defining a YTHDC1-MAFF-VMP1 axis protecting hepatocytes against oxidative stress in ischemia/reperfusion.

    Evidence YTHDC1/MAFF knockdown-overexpression with VMP1 rescue, in vitro H/R and in vivo I/R models

    PMID:40054588

    Open questions at the time
    • m6A sites on MAFF mRNA not mapped
    • Whether VMP1 is a direct MAFF target not shown
  18. 2025 Medium

    Added a BACH1-MAFF activation node for CLCF1-STAT3 signaling protecting hepatocytes in ischemia-reperfusion injury, reinforcing partner-dependent activator function.

    Evidence CUT&Tag, RNA-seq, adenoviral overexpression in mice, hepatocyte assays

    PMID:40169936

    Open questions at the time
    • Single lab
    • Contrast with BACH1-MAFF repressive contexts not reconciled
  19. 2025 Low

    Implicated upstream factors controlling MAFF nuclear access (ZNF655) and a tumor-suppressive MAFF effect on YAP1 nuclear translocation, though mechanisms are incompletely defined.

    Evidence ZNF655 depletion with MAFF translocation imaging and CCND1 rescue; YAP1 localization by IF and overexpression with xenografts

    PMID:41088232 PMID:41287850

    Open questions at the time
    • Methodological detail for ZNF655-MAFF promoter binding incomplete
    • Mechanism of MAFF suppression of YAP1 translocation not defined
    • Apparently opposite oncogenic vs tumor-suppressive roles not reconciled
  20. 2026 High

    Defined MAFF as a master metabolic regulator of ferroptosis, directly remodeling iron-handling (SLC11A2, NCOA4) and lipid metabolism genes to tune ferroptosis susceptibility and tumor behavior.

    Evidence RNA-seq, ChIP-seq, ferroptosis and lipid metabolite assays, loss/gain-of-function in breast cancer

    PMID:42209456

    Open questions at the time
    • Dimerization partner at these metabolic promoters not identified
    • How direction (pro- vs anti-ferroptotic) is set across tumor types unresolved
  21. 2026 Medium

    Extended MAFF's death-pathway control to necroptosis and divergent ferroptosis outcomes in pancreatic cancer via GATA4-MLKL repression and AKR1C1 activation.

    Evidence RNA-seq/GSEA with GATA4/MLKL knockdown and necroptosis inhibition; dual-luciferase for AKR1C1 with ferroptosis assays and xenografts

    PMID:41206944 PMID:42153582

    Open questions at the time
    • Why MAFF promotes vs inhibits ferroptosis in different tumors unresolved
    • Single lab per axis
  22. 2026 Medium

    Confirmed the NRF2-MAFF heterodimer directly drives contraction-associated genes (PTGS2, OXTR) downstream of melatonin/MT2/PKC in myometrium, returning to MAFF's earliest reproductive context.

    Evidence Dual-luciferase, siRNA, PKC inhibition, collagen gel contraction, in vivo sow parturition

    PMID:41854048

    Open questions at the time
    • Relative contribution of NRF2 vs MAFF to promoter occupancy not separated
    • Human relevance untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular rules determine whether a given MAFF dimer activates or represses a target, and which partner MAFF uses at each endogenous promoter across its many reported contexts.
  • No structural or cofactor model explaining context-dependent activation vs repression
  • Partner identity unassigned at most ChIP-defined target promoters
  • Opposing oncogenic and tumor-suppressive roles not mechanistically reconciled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 8 GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 1
Partners
BACH1BAP1BATF3NRF2

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 MafF encodes a small nuclear bZIP protein lacking the amino-terminal acidic transactivation domain present in c-Maf; when overexpressed via retroviral vector in CEF cells, MafF did not induce morphological transformation but induced colony formation in soft agar with very low efficiency; MafK protein was detected predominantly in nuclei by immunostaining. Retroviral overexpression in CEF cells, soft-agar colony assay, immunostaining with specific antibody, structural analysis of cDNA clones Oncogene Medium 8361754
1999 Human MafF (hMafF) binds specifically to the US-2 element in the oxytocin receptor (OTR) gene promoter, as shown by yeast one-hybrid screening and electrophoretic mobility shift assay (EMSA); hMafF is an 18-kDa protein with a leucine zipper but no transactivation domain, preferentially expressed in term myometrium. Yeast one-hybrid screening of term myometrium cDNA library, EMSA, Northern hybridization Biochemical and biophysical research communications Medium 10527846
1999 Murine MafF is dispensable for development: homozygous mafF null mice are born at normal Mendelian ratios with no obvious functional deficiencies, even in tissues where other small Maf proteins are low. The lacZ-knockin revealed prominent mafF expression in gut, lung, liver, heart outflow tract, cartilage, bone membrane, and skin, but not in hematopoietic cells at any developmental stage. mafF is regulated by three distinct promoters. Gene targeting (mafF null mice), lacZ knock-in reporter, developmental expression analysis The Journal of biological chemistry High 10409670
2002 MafF can form homodimers and high-affinity heterodimers with CNC-bZip family members Nrf1, Nrf2, and NF-E2. MafF homodimers do not repress transcription (unlike MafG/MafK homodimers) on gamma-globin, beta-globin, and GCSl promoters in multiple cell lines, while MafF/CNC heterodimers act as weak transcriptional activators. MafF shows a specific regulatory role in combination with Jun at the GCSl promoter. Reporter gene assays in multiple cell lines, protein–protein interaction studies, promoter-reporter constructs Blood cells, molecules & diseases Medium 12490281
2002 mafF transcript is differentially induced by electrophile-response-element (EpRE) activators PDTC and PEITC (but not tBHQ) in HepG2 cells, and this induction is transcriptionally mediated; mafF is induced to a greater extent than mafG or mafK. The induction by tBHQ failure suggests that small Maf upregulation is not an absolute requirement for EpRE-mediated gene expression. RT-PCR/Northern blot in multiple cell lines, actinomycin D transcription inhibition assay The Biochemical journal Medium 11772409
2005 MAFF mRNA and protein are rapidly induced (within 30 min) by IL-1β and TNF in PHM1-31 myometrial cells at the transcriptional level (actinomycin D-sensitive); the highly homologous MAFG and MAFK transcripts and proteins are not modulated by these cytokines, indicating a cytokine-specific regulation unique to MAFF. RT-PCR time-course, actinomycin D inhibition, Western blot with MAFF-specific antiserum Biology of reproduction Medium 16371591
2006 A novel protein MIP (MafF Interacting Protein) physically interacts with hMafF via its coiled-coil domain binding the leucine zipper of hMafF in vitro and in vivo; this interaction causes translocation of MIP from the cytoplasm to the nucleolus in HeLa cells. Co-expression of hMafF and MIP activates US2-element-driven transcription, whereas either alone has no effect, establishing MIP as a co-activator of hMafF. Co-immunoprecipitation (in vivo), in vitro binding assay, subcellular localization imaging, promoter-reporter assay in HeLa cells Archives of biochemistry and biophysics Medium 16549056
2009 Using a recombinant yeast detection system, MIP was confirmed to enable hMafF-dependent transactivation of US2-driven reporter (LacZ): only the co-presence of both MIP and hMafF activates the reporter, corroborating the co-activator role of MIP for hMafF. Recombinant yeast reporter system (beta-galactosidase quantitative assay), plasmid transformation of YM4271 yeast Journal of microbiological methods Low 19723544
2016 sMafs (MafF, MafG, MafK) are bZIP transcription factors that: (1) form homodimers that act as transcriptional repressors (lacking activation domain); (2) form obligatory heterodimers with CNC proteins (NF-E2 p45, Nrf1, Nrf2, Nrf3) and Bach proteins (Bach1, Bach2), which cannot bind DNA as monomers, making sMafs indispensable partners; (3) participate in transcriptional activation or repression depending on heterodimeric partner and context. Review synthesizing genetic analyses in mice, structural studies, and biochemical data across multiple labs Gene High 27058431
2019 MAFF directly binds the promoters of CXCL1 and CSF3 in PHM1-31 myometrial cells, as shown by ChIP, and MAFF knockdown significantly decreases CXCL1 and CSF3 transcript and protein levels. MAFF-dependent cytokine production in myometrial cells can modulate cytokine and matrix metalloproteinase gene expression in THP-1 monocytic cells in a paracrine manner. siRNA knockdown, ChIP, RT-PCR, ELISA, paracrine co-culture assay Journal of cellular and molecular medicine Medium 30669188
2021 MAFF forms a heterodimer with BACH1 that directly binds the LDLR promoter MAF recognition element (MARE) under inflammatory conditions (LPS stimulation), transcriptionally downregulating LDLR expression. Under non-inflammatory conditions, MAFF positively correlates with LDLR. BACH1 assists MAFF in inflammatory contexts, as revealed by ChIP-mass spectrometry. ChIP-sequencing, ChIP-mass spectrometry, siRNA knockdown, overexpression in mouse and human liver cells, KO mouse experiments, correlation in 600 CAD patients Circulation High 33626882
2021 MAFF heterodimerizes with BACH1 to directly activate IL11 transcription under hypoxic conditions in breast cancer cells; IL11 activates STAT3 signaling; inhibition of IL11 phenocopies MAFF inhibition in suppressing metastasis. MAFF expression is induced by hypoxia (HIF target). ChIP-sequencing, RNA-sequencing, siRNA knockdown, overexpression, invasion assay, metastasis mouse model Nature communications High 34262028
2021 MafF suppresses transcription from the HBV core promoter by physically binding to the HBV core promoter region (ChIP analysis) and competitively inhibiting HNF-4α binding to an overlapping sequence in enhancer II (EnhII). MafF loss (via CRISPR or siRNA) increases HBV core RNA and pgRNA levels. MafF expression is induced by IL-1β or TNF-α in an NF-κB-dependent manner in hepatocytes. siRNA library screen with HBV/NanoLuc reporter, CRISPR/Cas9 KO, ChIP analysis, overexpression with promoter mutation, siRNA in primary hepatocytes Journal of virology High 33980595
2021 miR-320a directly targets MafF mRNA (identified by RIP-Seq and confirmed by luciferase reporter assay), reducing MafF protein levels in pancreatic β cells; overexpression of miR-320a increases ROS, inhibits proliferation, and induces apoptosis of β cells, effects attributable to MafF suppression. RIP-Seq, luciferase reporter assay, Western blot, AAV8-mediated β cell-specific overexpression/inhibition, islet transplantation, hyperglycemic clamp Molecular therapy. Nucleic acids Medium 34631276
2024 BAP1 (a nuclear deubiquitinating enzyme) binds to MAFF and deubiquitylates it, primarily removing K48-linked ubiquitin chains, thereby stabilizing MAFF protein. Stabilized MAFF upregulates DUSP5 expression, resulting in inhibition of ERK phosphorylation, which suppresses colorectal cancer cell growth. Quantitative proteomics, DUB expression library screening, Co-IP, ubiquitination assay, RNA sequencing, gain-of-function/loss-of-function in CRC cells and xenografts European journal of cancer High 39151323
2024 MAFF directly regulates SLC7A11, CDK6, and CDKN2C transcription (by ChIP-seq), promoting ferroptosis (via SLC7A11 repression) and preventing cell cycle progression from G1 to S (via CDK6/CDKN2C). The cAMP/PKA/CREB1 pathway upregulates MAFF expression in response to cisplatin or ionizing radiation in LUAD. CRISPR screens (cell and murine models), single-cell RNA-seq, ChIP-seq, RNA-seq, cellular and xenograft models Drug resistance updates High 38266355
2024 MAFF binds to the ZNF711 promoter and, together with its interacting partner BATF3 (confirmed by co-IP and immunofluorescence co-localization), represses ZNF711 transcription; BATF3 knockdown alone or combined with MAFF knockdown produce similar effects on ZNF711 expression and apoptosis in ovarian cancer cells. Dual-luciferase reporter assay, ChIP-PCR, Co-IP, immunofluorescence, siRNA knockdown, xenograft model Chemico-biological interactions Medium 38908812
2025 HDAC6 suppresses MAFF expression through deacetylation of MAFF, removing its inhibitory effect on KLF5 transcription; MAFF directly represses KLF5 promoter activity (confirmed by ChIP and dual luciferase assay). Loss of MAFF-mediated KLF5 repression enhances fibrosis and inflammatory response in lupus nephritis. ChIP, dual luciferase reporter assay, cell transfection (overexpression/knockdown), in vivo MRL/lpr mouse model, biochemical analyses Renal failure Medium 39412062
2025 MAFF heterodimerizes with BACH1 to directly transcriptionally activate CLCF1 (identified by CUT&Tag + RNA-seq), which subsequently triggers STAT3 signaling; MAFF overexpression reduces hepatocyte apoptosis and inflammation in hepatic ischemia-reperfusion injury in mice. CUT&Tag sequencing, RNA-seq, adenovirus-mediated overexpression in mice, in vitro hepatocyte assays Cellular & molecular biology letters Medium 40169936
2025 YTHDC1 (m6A reader) mediates nuclear export and stabilization of MAFF mRNA and promotes MAFF translation; MAFF in turn transcriptionally activates VMP1. In hepatocytes, the YTHDC1-MAFF-VMP1 axis protects against oxidative stress in hepatic ischemia/reperfusion injury. Knockdown/overexpression of YTHDC1 and MAFF, VMP1 functional rescue, in vitro H/R model, in vivo I/R mouse model Cellular signalling Medium 40054588
2025 ZNF655 promotes nuclear translocation of MAFF in ovarian cancer cells; nuclear MAFF then directly binds the CCND1 promoter and transcriptionally activates CCND1, promoting cell proliferation and stemness. Rescue experiments confirm CCND1 is required for ZNF655-dependent effects. ZNF655 depletion, MAFF nuclear translocation analysis (immunofluorescence), promoter binding (ChIP implied by 'direct binding'), rescue experiments, xenograft models Cancer cell international Low 41088232
2025 MAFF suppresses YAP1 nuclear translocation in NSCLC cells; MAFF overexpression reduces YAP1, VEGF, and CTGF expression and inhibits angiogenesis both in vitro and in nude mouse xenograft models. Western blot, immunofluorescence (YAP1 localization), overexpression experiments, xenograft mouse model, IHC of clinical samples PeerJ Low 41287850
2026 MAFF directly transcriptionally activates SLC11A2 and NCOA4 (expanding the labile iron pool) and represses CPT2, FASN, and SCD1 (shifting lipid metabolism toward PUFAs), as established by combined RNA-seq and ChIP-seq; these metabolic changes promote ferroptosis susceptibility and tumor invasion in breast cancer cells. RNA-sequencing, ChIP-sequencing, functional ferroptosis assays, lipid metabolite measurement, loss-of-function/gain-of-function experiments Cell death & disease High 42209456
2026 MAFF acts as a direct transcriptional repressor of GATA4; GATA4 in turn transcriptionally activates MLKL (necroptotic executioner). MAFF depletion reactivates the GATA4-MLKL axis, triggering necroptosis in pancreatic cancer cells. Pharmacological inhibition of necroptosis or knockdown of GATA4/MLKL reverses the growth-inhibitory effects of MAFF silencing. RNA-sequencing, GSEA, MAFF KO/overexpression, genetic knockdown of GATA4 and MLKL, pharmacological necroptosis inhibition, in vivo tumor models Cancer science Medium 42153582
2026 MAFF directly binds the promoter of AKR1C1 and transcriptionally activates it (confirmed by dual-luciferase reporter assay); the MAFF-AKR1C1 axis leads to MDA accumulation and elevated lipid ROS, inhibiting ferroptosis and promoting pancreatic cancer progression. Dual-luciferase reporter assay, bioinformatics (ELMER), in vitro cellular assays, xenograft models, transcriptome sequencing QJM Medium 41206944
2026 In sow myometrium, NRF2 and MAFF directly target the promoters of PTGS2 and OXTR (contraction-associated genes), confirmed by dual-luciferase reporter assays; melatonin acting through the MT2 receptor activates PKC, which regulates NRF2 and MAFF expression to enhance myometrial contractility. Silencing MAFF in melatonin-treated cells reduces contraction-associated protein expression. Dual-luciferase reporter assay, siRNA knockdown, PKC pathway inhibition, collagen gel contraction assay, in vivo sow parturition experiments Journal of pineal research Medium 41854048

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 Small Maf proteins (MafF, MafG, MafK): History, structure and function. Gene 199 27058431
1993 Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. Oncogene 162 8361754
2012 The small MAF transcription factors MAFF, MAFG and MAFK: current knowledge and perspectives. Biochimica et biophysica acta 127 22721719
2021 The HIF target MAFF promotes tumor invasion and metastasis through IL11 and STAT3 signaling. Nature communications 100 34262028
2024 MAFF confers vulnerability to cisplatin-based and ionizing radiation treatments by modulating ferroptosis and cell cycle progression in lung adenocarcinoma. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 69 38266355
1999 Characterization of the murine mafF gene. The Journal of biological chemistry 56 10409670
2021 Transcription Factor MAFF (MAF Basic Leucine Zipper Transcription Factor F) Regulates an Atherosclerosis Relevant Network Connecting Inflammation and Cholesterol Metabolism. Circulation 48 33626882
2005 Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells. Biology of reproduction 45 16371591
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
2020 MafF Is Regulated via the circ-ITCH/miR-224-5p Axis and Acts as a Tumor Suppressor in Hepatocellular Carcinoma. Oncology research 33 31969212
2002 Differential induction of mafF, mafG and mafK expression by electrophile-response-element activators. The Biochemical journal 33 11772409
1999 Molecular cloning of a human MafF homologue, which specifically binds to the oxytocin receptor gene in term myometrium. Biochemical and biophysical research communications 32 10527846
2016 Reclassification of strains MAFF 303099T and R7A into Mesorhizobiumjaponicum sp. nov. International journal of systematic and evolutionary microbiology 29 27565417
2021 miR-320a induces pancreatic β cells dysfunction in diabetes by inhibiting MafF. Molecular therapy. Nucleic acids 26 34631276
2019 Regulation of CXCL1 chemokine and CSF3 cytokine levels in myometrial cells by the MAFF transcription factor. Journal of cellular and molecular medicine 22 30669188
2020 Responsive Expression of MafF to β-Amyloid-Induced Oxidative Stress. Disease markers 20 33488846
2021 MafF Is an Antiviral Host Factor That Suppresses Transcription from Hepatitis B Virus Core Promoter. Journal of virology 19 33980595
2020 RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway. Molecular therapy oncolytics 17 32322670
2002 Cloning MafF by recognition site screening with the NFE2 tandem repeat of HS2: analysis of its role in globin and GCSl genes regulation. Blood cells, molecules & diseases 16 12490281
2021 Proteome-scale profiling reveals MAFF and MAFG as two novel key transcription factors involved in palmitic acid-induced umbilical vein endothelial cell apoptosis. BMC cardiovascular disorders 15 34535081
2019 Association between genetic polymorphisms of NRF2, KEAP1, MAFF, MAFK and anti-tuberculosis drug-induced liver injury: a nested case-control study. Scientific reports 14 31586142
2018 Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion. International journal of molecular sciences 13 29757260
2024 BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer. European journal of cancer (Oxford, England : 1990) 12 39151323
2006 The novel human gene MIP functions as a co-activator of hMafF. Archives of biochemistry and biophysics 11 16549056
1997 DNA modification in carcinogen risk assessment in relation to diet: recent advances and some perspectives from a MAFF workshop. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 9 23889108
1992 Transformation of opium poppy (Papaver somniferum L.) with Agrobacterium rhizogenes MAFF 03-01724. Plant cell reports 9 24213545
2017 System modeling reveals the molecular mechanisms of HSC cell cycle alteration mediated by Maff and Egr3 under leukemia. BMC systems biology 8 28984203
2025 MAFF alleviates hepatic ischemia-reperfusion injury by regulating the CLCF1/STAT3 signaling pathway. Cellular & molecular biology letters 7 40169936
2024 HDAC6 promotes inflammation in lupus nephritis mice by regulating transcription factors MAFF and KLF5 in renal fibrosis. Renal failure 7 39412062
2024 MAFF mediates PEITC-induced enhancement of sensitivity to carboplatin in ovarian cancer cell lines via activating ZNF711 transcription in vivo and invitro. Chemico-biological interactions 4 38908812
2007 In silico restriction landmark genome scanning analysis of Xanthomonas oryzae pathovar oryzae MAFF 311018. Biochemical and biophysical research communications 4 17904519
2025 m6A reader YTHDC1 mediates MAFF nuclear export to induce VMP1 transcription and alleviate I/R-induced oxidative stress injury in hepatocytes. Cellular signalling 2 40054588
2026 MAFF drives pancreatic cancer progression through AKR1C1-mediated inhibition of ferroptosis. QJM : monthly journal of the Association of Physicians 1 41206944
2025 The effects of hepatocyte-specific MafF overexpression on FFA or ETOH induced hepatocyte steatosis and its underlying mechanism. Hepatology forum 1 40686592
2009 Establish a recombinant yeast detection system to study the effect of MIP on transactivation function of hMafF in US2-driven gene transcription. Journal of microbiological methods 1 19723544
2026 Melatonin Enhances the Myometrial Contraction Through MT2-PKC-NRF2/MAFF Signaling Pathway in Sows. Journal of pineal research 0 41854048
2026 MAFF Suppresses Necroptosis in Pancreatic Cancer via the GATA4-MLKL Axis. Cancer science 0 42153582
2026 MAFF regulates ferroptotic sensitivity through iron homeostasis and fatty acid synthesis. Cell death & disease 0 42209456
2025 Immunosenescence-Related Gene MAFF is Involved in Immune Regulation and Malignant Progression in Pancreatic Adenocarcinoma. Biological procedures online 0 40665213
2025 MAFF mitigates oxidative stress and pyroptosis in cardiopulmonary bypass-induced myocardium injury. Frontiers in physiology 0 40821946
2025 Targeted and personalized immunotherapy in lung adenocarcinoma: single-cell RNA sequencing of MAFF+ tumor cells and the therapeutic potential of FOS. Frontiers in immunology 0 40936936
2025 ZNF655 promotes tumor growth and chemoresistance by targeting MAFF-CCND1 axis in ovarian cancer. Cancer cell international 0 41088232
2025 MAFF inhibits angiogenesis in non-small cell lung cancer by suppressing YAP1 nuclear translocation. PeerJ 0 41287850

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