Affinage

MAF1

Repressor of RNA polymerase III transcription MAF1 homolog · UniProt Q9H063

Length
256 aa
Mass
28.8 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAF1 is a conserved master repressor of RNA polymerase III transcription that integrates nutrient, stress, and growth-factor signaling to control biosynthetic capacity, lipid metabolism, and cell proliferation. Under favorable growth conditions, mTORC1 (and in yeast PKA and CK2) phosphorylates MAF1 at multiple sites (S60, S68, S75), promoting its cytoplasmic retention and CUL2-mediated ubiquitin–proteasomal degradation; stress or nutrient limitation triggers PP2A- and PP4-dependent dephosphorylation, nuclear accumulation, and direct engagement of the Pol III clamp, where MAF1 seals the active-site cleft, displaces the C82/34/31 subcomplex, and competitively excludes TFIIIB from promoter DNA, thereby blocking transcription initiation of tRNA, 5S rRNA, and other Pol III targets genome-wide (PMID:12504022, PMID:20887893, PMID:32066962, PMID:20516213, PMID:22333918, PMID:31645432). SUMOylation at K35, reversed by SENP1, is independently required for MAF1 association with Pol III and promoter recruitment (PMID:23673667). In mammalian cells, MAF1 additionally functions as a Pol II transcriptional regulator—repressing TBP and FASN (opposing SREBP1c-driven lipogenesis) and activating PTEN transcription—thereby linking Pol III repression to PI3K/AKT signaling, lipid homeostasis, and tumor suppression, as demonstrated by resistance to diet-induced obesity in Maf1-knockout mice and suppression of tumorigenesis upon MAF1 overexpression (PMID:17499043, PMID:25502566, PMID:26910647, PMID:25934505).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2002 High

    Identification of Maf1 as a dedicated Pol III repressor resolved how diverse stress signals converge on a single target—TFIIIB—to shut down Pol III transcription.

    Evidence Genetic epistasis and TFIIIB–DNA assembly assays in S. cerevisiae under rapamycin, DNA damage, and secretory stress

    PMID:12504022

    Open questions at the time
    • Mechanism of TFIIIB inhibition not resolved at molecular level
    • Kinases and phosphatases controlling Maf1 unknown
    • Whether Maf1 contacts Pol III directly was untested
  2. 2004 High

    Demonstration that Maf1 inhibits both de novo TFIIIB assembly and Pol III recruitment to preformed complexes, and physically contacts Brf1 and Pol III, established a two-step repression mechanism.

    Evidence In vitro transcription with recombinant Maf1, co-immunoprecipitation in yeast

    PMID:15590667

    Open questions at the time
    • Structural basis of Maf1–Pol III interaction unknown
    • Whether Maf1 functions genome-wide was not addressed
  3. 2006 High

    Genome-wide ChIP and phosphorylation studies established that Maf1 is a global Pol III repressor whose nuclear localization and activity are controlled by a phosphorylation switch: PKA phosphorylation retains Maf1 in the cytoplasm, while PP2A-mediated dephosphorylation drives nuclear import and Pol III association.

    Evidence ChIP-chip, subcellular fractionation, PP2A and PKA mutant analyses, phosphosite mutagenesis in S. cerevisiae

    PMID:16762835 PMID:16762836 PMID:17005718

    Open questions at the time
    • Identity of phosphatase(s) beyond PP2A uncertain
    • Mechanism by which phosphorylation directly controls repressor activity in the nucleus unclear
    • Relevance to mammalian cells untested
  4. 2007 High

    Extension to human cells revealed that MAF1 represses not only Pol III but also Pol I and Pol II transcription—including TBP itself—broadening its role from a Pol III-specific factor to a multi-polymerase transcriptional regulator with tumor-suppressive properties.

    Evidence ChIP, reporter assays, gain/loss-of-function in glioblastoma lines; co-IP of MAF1 with human Brf1 and Brf2

    PMID:17499043 PMID:17505538

    Open questions at the time
    • Mechanisms of Pol I and Pol II repression not molecularly defined
    • In vivo tumor-suppressor function not yet tested in animal models
  5. 2008 High

    In vitro reconstitution with human factors and identification of the yeast exportin Msn5 clarified that phosphorylated Maf1 is actively exported from the nucleus and that Maf1 blocks new Pol III recruitment but cannot displace preformed initiation or elongation complexes.

    Evidence Immobilized template transcription assay with recombinant human MAF1; Msn5 co-IP and msn5Δ analysis in yeast

    PMID:18377933 PMID:18445601 PMID:18974046

    Open questions at the time
    • How cells clear pre-engaged Pol III from active genes under acute stress remained unresolved
    • Mammalian export mechanism not identified
  6. 2010 High

    Three concurrent studies demonstrated that mTORC1 directly phosphorylates MAF1 at S60/S68/S75 to relieve Pol III repression, establishing the mTOR–MAF1 axis as the central nutrient-sensing mechanism controlling Pol III output in mammalian cells.

    Evidence In vitro mTORC1 kinase assays, phosphosite mutagenesis, ChIP, rapamycin/Torin1 treatment in human cells

    PMID:20233713 PMID:20516213 PMID:20543138

    Open questions at the time
    • Whether mTOR-dependent phosphorylation also regulates MAF1 stability was unknown
    • Functional consequences of individual phosphosites not fully separated
  7. 2010 High

    Crystal structure of Maf1 and cryo-EM of the Pol III–Maf1 complex revealed the structural mechanism: Maf1 binds the Pol III clamp, rearranges C82/34/31, seals the active-site cleft, and overlaps with the TFIIIB binding surface, explaining how it blocks closed-complex formation.

    Evidence X-ray crystallography (Maf1) and cryo-EM (Pol III–Maf1, Pol III–DNA–RNA) with functional validation

    PMID:20887893

    Open questions at the time
    • Resolution limited; a near-atomic-resolution structure was still needed
    • Intramolecular domain rearrangement upon phosphorylation not structurally captured
  8. 2011 High

    Identification of CK2 as a kinase that phosphorylates Maf1 to release it from Pol III at tRNA genes provided the reactivation arm of the Pol III phosphorylation cycle.

    Evidence In vitro CK2 kinase assay on human and yeast Maf1, ChIP, CK2 inhibitor treatment in yeast

    PMID:21383183

    Open questions at the time
    • CK2 phosphosites on Maf1 not mapped
    • Whether CK2 functions analogously in mammalian Maf1 reactivation untested
  9. 2012 High

    Identification of the PP4 complex (Pph3/Psy2/Rrd1/Tip41) as the principal Maf1 phosphatase resolved how stress signals trigger rapid Maf1 dephosphorylation and nuclear entry.

    Evidence In vitro phosphatase assay with purified PP4, co-IP, PP4 subunit mutant analysis in yeast

    PMID:22333918

    Open questions at the time
    • PP4 regulation of mammalian MAF1 not demonstrated
    • How PP4 is itself activated by diverse stresses remained unclear
  10. 2013 High

    Discovery of MAF1 SUMOylation at K35 (reversed by SENP1) established a phosphorylation-independent regulatory layer required for MAF1 association with Pol III and promoter recruitment.

    Evidence K35R mutagenesis, SUMOylation assays, ChIP, SENP1 functional analysis in human cells

    PMID:23673667

    Open questions at the time
    • Structural basis of how SUMOylation enables Pol III binding unknown
    • Upstream signals controlling MAF1 SUMOylation not identified
  11. 2014 High

    Demonstration that MAF1 directly binds and represses the FASN promoter (opposing SREBP1c) and is transcriptionally regulated by PTEN/PI3K/AKT/FoxO1 signaling linked MAF1 to lipid metabolism and tumor suppression in vivo.

    Evidence ChIP, promoter reporter assays, mouse tumor xenograft models, diet-induced PI3K pathway activation

    PMID:25502566

    Open questions at the time
    • Other lipogenic gene targets of MAF1 not mapped genome-wide
    • Mechanism of MAF1 action at Pol II promoters distinct from Pol III repression not defined
  12. 2015 High

    Maf1 knockout mice showed resistance to diet-induced obesity despite elevated precursor tRNA synthesis with unchanged mature tRNA levels, revealing a metabolically costly futile tRNA cycle that increases energy expenditure, NAD+, and autophagy.

    Evidence Maf1-/- whole-body KO mouse model with metabolic phenotyping and precursor tRNA quantification

    PMID:25934505

    Open questions at the time
    • Mechanism coupling futile tRNA cycling to NAD+ elevation not molecularly defined
    • Contribution of non-Pol III MAF1 targets to metabolic phenotype not separated
  13. 2016 High

    MAF1 was shown to activate PTEN transcription and its genome-wide occupancy was mapped by ChIP-seq, confirming that MAF1 predominantly occupies Pol III loci and dynamically increases association with transcribing Pol III upon mTORC1 inhibition, while also functioning at select Pol II promoters.

    Evidence ChIP-seq in human fibroblasts, nascent small RNA sequencing, ChIP at PTEN promoter, cancer models

    PMID:26910647 PMID:26941251

    Open questions at the time
    • How MAF1 switches from Pol III repressor to Pol II activator at PTEN mechanistically unresolved
    • Whether MAF1 genome occupancy changes in cancer contexts not profiled
  14. 2019 High

    Discovery that mTORC1 phosphorylation at S75 enhances CUL2-mediated ubiquitination and proteasomal degradation of MAF1 revealed a protein-stability layer by which mTOR signaling derepresses Pol III.

    Evidence Ubiquitination assays, CUL2 knockdown, proteasome inhibition, phosphomutant analysis in hepatocellular carcinoma cells

    PMID:31645432

    Open questions at the time
    • Other E3 ligases or deubiquitinases regulating MAF1 not identified
    • Whether CUL2 pathway operates in non-cancer cells unknown
  15. 2020 High

    A 3.3-Å cryo-EM structure of yeast Maf1–Pol III provided near-atomic detail of the repression mechanism: Maf1 engages the C34 winged-helix-2 domain, seals the active site, and overlaps the TFIIIB binding surface in the preinitiation complex.

    Evidence Cryo-EM at 3.3-Å resolution of the yeast Pol III–Maf1 complex

    PMID:32066962

    Open questions at the time
    • Structure of phosphorylated or SUMOylated Maf1 not determined
    • Human Pol III–MAF1 structural complex not available
  16. 2022 High

    Conditional MAF1 overexpression in mesenchymal lineage cells increased bone mass and osteoblastogenesis, demonstrating that MAF1-mediated Pol III repression influences differentiation through tRNA-dependent translational control.

    Evidence Prx1-Cre;LSL-MAF1 conditional OE and Maf1-/- KO mice, ex vivo osteoblastogenesis assays, RNA-seq

    PMID:35611941

    Open questions at the time
    • Direct evidence for codon-usage-dependent translational regulation by MAF1-altered tRNA pools not provided
    • Whether osteoblast phenotype is Pol III-dependent or reflects Pol II targets of MAF1 untested
  17. 2024 Medium

    MAF1 was found to regulate Grin1 (NMDAR1) expression by direct promoter binding, linking MAF1 to calcium homeostasis and synaptic remodeling; conditional Maf1 KO improved cognition in an Alzheimer's disease mouse model.

    Evidence ChIP-PCR at Grin1 promoter, luciferase reporter, conditional KO in Alzheimer's model mice, calcium imaging

    PMID:38226680

    Open questions at the time
    • Single-lab study; independent replication needed
    • Mechanism by which MAF1 activates or represses Grin1 transcription not resolved
    • Whether neuronal MAF1 functions primarily through Pol III or Pol II targets is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how MAF1 mechanistically switches between Pol III repressor, Pol II repressor, and Pol II activator functions; the structural basis of phosphorylation- and SUMOylation-dependent conformational changes; and the relative contributions of Pol III versus Pol II target regulation to organismal phenotypes in metabolism, neuroplasticity, and cancer.
  • No structure of phosphorylated or SUMOylated MAF1
  • Genome-wide map of Pol II targets directly bound by MAF1 lacking
  • Tissue-specific relative importance of Pol III vs Pol II repression unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0098772 molecular function regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 3
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-162582 Signal Transduction 7 R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 3
Partners
BRF1BRF2CSNK2A1CUL2MTORPOLR3APPH3SENP1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Maf1 is an essential mediator of RNA polymerase III transcriptional repression in S. cerevisiae, required for repression in response to rapamycin-induced nutrient limitation, DNA damage, and secretory pathway defects. Biochemically, Maf1-dependent repression targets TFIIIB, with a defect in TFIIIB-DNA complex assembly under repressing conditions. Genetic epistasis (signaling pathway analysis), biochemical studies (TFIIIB-DNA complex assembly assay) Molecular cell High 12504022
2004 Maf1-dependent repression of Pol III transcription in yeast involves two steps: inhibition of de novo TFIIIB assembly onto DNA and inhibition of Pol III recruitment to preassembled TFIIIB-DNA complexes. Maf1 physically interacts with Brf1 and Pol III, as shown by co-immunoprecipitation, and acts by a non-stoichiometric mechanism. In vitro transcription assays with yeast extracts, co-immunoprecipitation, recombinant Maf1 inhibition assays The Journal of biological chemistry High 15590667
2006 Maf1 is a general and direct repressor of all yeast Pol III-transcribed genes genome-wide. Under repressing conditions (rapamycin), Maf1 is dephosphorylated and accumulates in the nucleus, directly interacting with the largest Pol III subunit C160. Protein phosphatase type 2A (PP2A) is required for rapamycin-induced Maf1 dephosphorylation, nuclear accumulation, and Pol III repression. ChIP-chip (genome-wide), co-immunoprecipitation, PP2A mutant analysis, phosphorylation state analysis Molecular cell High 16762835
2006 Maf1 is phosphorylated under favorable growth conditions and rapidly dephosphorylated under diverse stress/nutrient-limitation conditions, leading to nuclear localization, physical association with Pol III, and targeting to Pol III-transcribed genes genome-wide. Maf1 mutants defective in dephosphorylation fail to accumulate in the nucleus and cannot associate with Pol III. ChIP-chip, phosphorylation state analysis, subcellular fractionation, co-immunoprecipitation, Maf1 phosphomutant analysis Molecular cell High 16762836
2006 Protein kinase A (PKA) negatively regulates Maf1 function in yeast by phosphorylating it in vitro and in vivo, inhibiting nuclear import of Maf1 via the N-terminal nuclear localization sequence. Strains with high PKA activity block Pol III repression; strains lacking PKA are hyperrepressible. A PKA-independent step is also required for nuclear Maf1 to repress Pol III. In vitro kinase assay (PKA phosphorylation of Maf1), in vivo phosphorylation analysis, PKA activity manipulation, nuclear localization analysis, phosphosite mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 17005718
2007 Human Maf1 negatively regulates transcription by all three nuclear RNA polymerases (Pol I, II, and III). Maf1 represses Pol I- and Pol III-dependent transcription directly, and represses Pol II transcription in part by targeting an Elk-1-binding site in the TBP promoter. Maf1 occupancy at Pol III genes is inversely correlated with TFIIIB and Pol III occupancy. Maf1 overexpression suppresses anchorage-independent growth. ChIP, luciferase reporter assays, RNA analysis in glioblastoma cell lines, gain/loss-of-function experiments Molecular cell High 17499043
2007 Human Maf1 represses Pol III transcription in vivo through physical interaction with the TFIIB family members Brf1 and Brf2, components of TFIIIB. In vivo luciferase reporter assay, co-immunoprecipitation International journal of biological sciences Medium 17505538
2008 Mammalian Maf1 represses Pol III transcription in vitro and in transfected fibroblasts; genetic deletion of Maf1 elevates Pol III transcript levels. Maf1 interacts with Pol III and TFIIIB and is phosphorylated in a serum-sensitive manner in vivo. In vitro transcription assay, genetic KO fibroblasts, co-immunoprecipitation, ChIP, phosphorylation analysis Journal of molecular biology High 18377933
2008 In yeast, nuclear export of phosphorylated Maf1 is dependent on the exportin Msn5; Maf1 physically interacts with Msn5. Phosphorylation of Maf1 inside the nucleus acts both directly to relieve Pol III repression and indirectly by stimulating Msn5-mediated nuclear export. Co-immunoprecipitation, subcellular fractionation/localization, msn5Δ mutant analysis, phosphomutant analysis The Journal of biological chemistry High 18445601
2008 In a human Pol III in vitro system, recombinant Maf1 inhibits recruitment of TFIIIB and Pol III to immobilized templates. However, Pol III bound in preinitiation or elongation complexes is protected from Maf1 repression, and Maf1 cannot inhibit facilitated recycling, indicating additional biochemical steps are required for rapid repression in vivo. Immobilized template transcription assay (in vitro), recombinant human Maf1 The Journal of biological chemistry High 18974046
2009 In yeast, hydrogen peroxide-induced nuclear accumulation of Maf1 requires cytoplasmic thioredoxins Trx1 and Trx2, and PP2A phosphatase activity is required for H2O2-induced Maf1 dephosphorylation and nuclear accumulation, independent of PKA downregulation. Subcellular localization analysis, thioredoxin mutant analysis, PP2A inhibitor/mutant analysis, phosphorylation state analysis Eukaryotic cell Medium 19581440
2010 mTOR associates with TFIIIC via a TOR signaling motif on TFIIIC and localizes to tRNA and 5S rRNA gene loci. mTOR phosphorylates Maf1 at serine 75 in vitro and in vivo, relieving Pol III repression. In HeLa cells, unlike in yeast, no nuclear export of Maf1 occurs in response to mTOR signaling. Proximity ligation assay, in vitro kinase assay (mTOR phosphorylation of Maf1 at S75), ChIP, in vivo phosphorylation analysis Proceedings of the National Academy of Sciences of the United States of America High 20543138
2010 mTORC1 directly phosphorylates human MAF1 mainly at residues S60, S68, and S75, inhibiting its Pol III repression function. MAF1 is absolutely required for Pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. Phosphorylation at these sites negatively regulates MAF1 repressor activity. In vitro kinase assay (mTORC1 directly phosphorylating MAF1), phosphosite mutagenesis (S60A, S68A, S75A), RNAi knockdown, Pol III transcription assays Molecular and cellular biology High 20516213
2010 mTOR inhibition leads to dephosphorylation of Maf1 at Ser-75, nuclear accumulation, increased Maf1 occupancy at Pol III-dependent genes, and concomitant reduction in Pol III and Brf1 binding. Maf1 phosphomutants (S75A, 4A) progressively enhance basal repression of tRNA transcription. mTORC1 itself associates with Pol III gene loci. Quantitative phosphoproteomics, ChIP, phosphosite mutagenesis, RNAi knockdown, pre-tRNA quantification The Journal of biological chemistry High 20233713
2010 Crystal structure of Maf1 and cryo-EM structures of Pol III, active Pol III-DNA-RNA complex, and repressive Pol III-Maf1 complex reveal that Maf1 binds the Pol III clamp and rearranges the Pol III-specific subcomplex C82/34/31 at the rim of the active center cleft, impairing Pol III recruitment to promoter DNA-TFIIIB-TBP complexes and preventing closed complex formation, without impairing RNA synthesis from a preformed scaffold. X-ray crystallography (Maf1 structure), cryo-EM (Pol III-Maf1 complex), functional validation Cell High 20887893
2010 Full repression of Pol III transcription requires interaction between the two conserved domains of Maf1. The N-terminal and C-terminal domains of human Maf1 interact with each other (pulldown, size-exclusion chromatography); yeast Maf1 domains interact in two-hybrid assay. Integrity of both domains and their direct interaction are necessary for Maf1 dephosphorylation and inhibition of Pol III transcription. Pull-down assay, size-exclusion chromatography, yeast two-hybrid, limited proteolysis, functional complementation The Journal of biological chemistry High 20817737
2011 Casein kinase II (CK2) phosphorylates Maf1 in vitro (both human and yeast Maf1 by recombinant human and yeast CK2). CK2 activity is required for the release of Maf1 from Pol III at tRNA genes and for subsequent tRNA transcription activation when yeast shift from repressive to favorable conditions. CK2 associates with tRNA genes, and its association is enhanced in the absence of Maf1. In vitro kinase assay (CK2 phosphorylating Maf1), ChIP, CK2 inhibitor treatment, maf1Δ epistasis Proceedings of the National Academy of Sciences of the United States of America High 21383183
2012 Protein phosphatase 4 (PP4) complex (catalytic subunit Pph3, scaffold Psy2, regulatory subunits Rrd1/Tip41) is the main Maf1 phosphatase in yeast. A portion of PP4 co-precipitates with Maf1, and purified PP4 dephosphorylates Maf1 in vitro. PP4 activity is required for Maf1 nuclear localization and rapid Pol III repression in response to diverse stresses. In vitro phosphatase assay (purified PP4 dephosphorylating Maf1), co-immunoprecipitation, genetic analysis of PP4 subunit mutants, nuclear localization assay The EMBO journal High 22333918
2013 Maf1 is SUMOylated by both SUMO1 and SUMO2, with Lys-35 as the major SUMOylation site; the deSUMOylase SENP1 controls Maf1K35 SUMOylation. SUMOylation at K35 is required for Maf1's ability to associate with Pol III and to be recruited to tRNA gene promoters; SUMOylation is independent of mTOR-dependent phosphorylation. SUMOylation does not alter Maf1 subcellular localization but is required for Pol III dissociation from gene promoters. Mutagenesis (K35R and other Lys mutants), SUMOylation assays, ChIP, co-immunoprecipitation, SENP1 functional analysis The Journal of biological chemistry High 23673667
2014 Maf1 is a downstream target of PTEN/PI3K/AKT/FoxO1 signaling. PTEN-mediated changes in Maf1 expression are mediated through PI3K/AKT/FoxO1 signaling. Maf1 occupies the FASN promoter and opposes SREBP1c-mediated transcription, thereby inhibiting intracellular lipid accumulation. Maf1 reduces anchorage-independent growth and tumor formation in mice. ChIP, gene reporter assay, mouse tumor models, in vivo diet-induced PI3K activation, genetic KO/KD PLoS genetics High 25502566
2015 Whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity. Loss of Maf1 increases precursor tRNA synthesis without significant effects on mature tRNA levels, implying a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Maf1-/- mice show increased NAD+ levels and elevated autophagy via spermidine. Maf1 knockout mouse model, metabolic measurements, precursor tRNA analysis, metabolite profiling Genes & development High 25934505
2015 MAF1 represses CDKN1A (p21) expression through a Pol III-dependent mechanism. MAF1 knockdown induces CDKN1A transcription concurrent with Pol III recruitment; simultaneous knockdown of Pol III or BRF1 abolishes this activation, indicating Pol III recruitment is required. MAF1 knockdown enhances binding of Pol III, BRF1, CFP1, p300, PCAF, TBP, and POLR2E to the CDKN1A promoter. ChIP, RNAi knockdown (MAF1, Pol III, BRF1), gene expression analysis, ChIP after sequential KD eLife High 26067234
2016 MAF1 binds to the PTEN promoter, enhancing PTEN promoter acetylation and activity, functioning as a transcriptional activator of PTEN. MAF1 downregulation paradoxically leads to activation of AKT-mTOR signaling through decreased PTEN expression. MAF1 displays tumor-suppressor activity in hepatocellular carcinoma models. ChIP, luciferase promoter reporter assay, gene KD/OE, in vitro and in vivo cancer models Hepatology High 26910647
2016 Human MAF1 genome-wide occupancy in human fibroblasts is largely confined to Pol III loci even under serum-replete conditions, and MAF1 increasingly targets transcribing Pol III in response to serum starvation in an mTORC1-dependent manner. MAF1 prevents Pol III recruitment rather than inducing long-term transcriptional arrest. ChIP-seq, EU-labeling with sequencing of nascent small RNAs, genome-wide Pol III occupancy profiling Genome research High 26941251
2018 Ras/ERK signaling promotes Pol III-mediated tRNA synthesis in Drosophila by phosphorylating and inhibiting nuclear localization and function of the Pol III repressor Maf1. Pol III function is required for Ras/ERK-driven proliferation in epithelial and stem cells; Myc is required but not sufficient for Ras-mediated tRNA stimulation. Genetic epistasis in Drosophila, in vivo tRNA synthesis assay, nuclear localization analysis, ERK pathway manipulation PLoS genetics High 29401457
2018 Maf1 and repression of Pol III-mediated transcription promote induction of mouse embryonic stem cells into mesoderm and adipocyte differentiation. Pol III-mediated transcription positively regulates long non-coding RNA H19 and Wnt6, established adipogenesis inhibitors. Reduced Maf1 expression impairs adipogenesis. Maf1 KD/OE in mESCs and preadipocytes, Brf1 KD, chemical Pol III inhibition, RNA-seq, adipogenesis assays Cell reports Medium 30110641
2019 MAF1 ubiquitination is enhanced upon mTORC1-mediated phosphorylation at Ser-75, and the E3 ubiquitin ligase CUL2 critically regulates MAF1 ubiquitination and protein stability. Loss of MAF1 due to proteasomal degradation derepresses Pol III transcription and modulates doxorubicin sensitivity in hepatocellular carcinoma. Ubiquitination assays, proteasome inhibitor experiments, CUL2 KD, phosphomutant analysis, Pol III transcription assays The Journal of biological chemistry High 31645432
2019 Maf1 mediates mTOR signaling to regulate Pol III-dependent tRNA transcription in cardiac cardiomyocytes. Maf1 directly binds ERK1/2 by co-immunoprecipitation, and ERK1/2 regulates Pol III transcription. Maf1 knockout exacerbates cardiac hypertrophy while Maf1 overexpression ameliorates it by inhibiting Pol III transcription via ERK1/2 suppression. Maf1 KO mouse model, adenoviral Maf1 OE, ERK inhibitor treatment, co-immunoprecipitation, Pol III transcription analysis, cardiac phenotype readouts Theranostics Medium 31695767
2020 Cryo-EM structure of yeast Maf1 bound to Pol III at 3.3-Å resolution shows Maf1 sequesters Pol III elements involved in transcription initiation, binds the mobile C34 winged helix 2 domain, seals off the active site, and overlaps with the TFIIIB binding site in the preinitiation complex. Cryo-EM structure determination (3.3-Å resolution) Nature structural & molecular biology High 32066962
2020 Maf1 directly binds to the NLRP3 gene promoter region and competitively regulates NLRP3 expression with NF-κB/p65, suppressing NLRP3 inflammasome activation and blood-brain barrier disruption in sepsis-associated encephalopathy. ChIP (promoter binding), luciferase reporter assay, NLRP3 OE rescue experiment, in vivo LPS model Frontiers in immunology Medium 33424842
2020 MAF1 functions as a chronic repressor of active Pol III loci in mouse liver in both fasted and refed conditions, and modulates pol III occupancy under different nutritional states. In Maf1-/- mice, Pol III occupancy and precursor tRNA levels are higher than wild-type in multiple organs regardless of fasting/refeeding. Pol III ChIP-seq, precursor tRNA quantification, Maf1 KO mouse model in fasting/refeeding paradigm Scientific reports High 32686713
2021 Maf1 mediates mTOR signaling to regulate Pol III-dependent rRNA and tRNA transcription in cortical neurons. mTOR regulates Maf1 phosphorylation and subcellular localization in neurons. Maf1 knockdown increases Pol III transcription, neurite outgrowth, and dendritic spine formation. In response to photothrombotic stroke, Maf1 expression increases and accumulates in nuclei of peri-infarct neurons, and Maf1 knockdown enhances neural plasticity and functional recovery. Maf1 binds promoters of CREB-associated genes involved in neural plasticity. AAV-mediated Maf1 KD in vivo, CUT&TAG-seq (genome-wide promoter binding), photothrombotic stroke model, live imaging of neuronal morphology Journal of advanced research High 36402285
2021 In C. elegans, mafr-1 deficiency in the absence of UV activates the DNA damage response (DDR), including phosphorylation of ATM/ATR target proteins. UV-induced intracellular lipid accumulation requires mafr-1, atm-1, and atl-1 (DDR apical kinases), placing Maf1 as a component of the DDR pathway for lipid homeostasis. Genetic epistasis in C. elegans (mafr-1 KO, atm-1/atl-1 mutants), UV dose-response, lipid accumulation assay, DDR marker analysis Molecular biology of the cell Medium 33788576
2022 MAF1 promotes osteoblast differentiation and regulates bone mass. MAF1 overexpression in mesenchymal lineage cells (Prx1-Cre;LSL-MAF1 mice) increases bone mass and enhances osteoblastogenesis. MAF1 induces genes known to promote osteoblast differentiation, and osteoblast-differentiating genes display codon bias, suggesting a tRNA-based translational mechanism. Conditional MAF1 OE mouse model, global Maf1 KO mouse, ex vivo osteoblastogenesis assay, RNA-seq eLife High 35611941
2024 Maf1 regulates the expression of NMDAR1 by binding to the promoter region of Grin1, further regulating calcium homeostasis and synaptic remodelling in neurons. Conditional KO of Maf1 in a mouse model of Alzheimer's disease restored learning and memory function. ChIP-PCR (Maf1 binding to Grin1 promoter), luciferase reporter assay, conditional KO mouse model, calcium imaging Brain : a journal of neurology Medium 38226680
2024 Bud27 (a prefoldin-like protein) regulates Maf1 phosphorylation and nuclear localization by associating with the Maf1 phosphatase PP4 in vivo. Lack of Bud27 decreases the PP4-Maf1 interaction, reduces Maf1 dephosphorylation, and impairs Maf1 nuclear entry, thereby affecting Pol III transcription repression. Co-immunoprecipitation (Bud27-PP4 interaction), phosphorylation state analysis, subcellular localization, genetic analysis Nucleic acids research Medium 38864693
2024 Progesterone receptor (PR) co-recruits with Maf1 to approximately half of Pol III-occupied tRNA genes upon progestin treatment and specifically represses approximately one-third of highly expressed tRNA genes. Maf1 knockdown significantly reduces PR-mediated tRNA transcription downregulation, demonstrating that Maf1 is necessary for PR-mediated Pol III repression. ChIP-seq (PR, POLR3A, Brf1, Maf1), nascent tRNA transcription assay, Maf1 RNAi knockdown epistasis bioRxivpreprint Medium 39763804
2015 MAF1 interacts with PCNA in human cells, as identified by bimolecular fluorescence complementation screen and validated by co-immunoprecipitation from human cell extracts and with recombinant proteins, suggesting a potential role for MAF1 in DNA replication or repair. Bimolecular fluorescence complementation (BiFC) screen, co-immunoprecipitation from human cell extracts, recombinant protein interaction analysis Cell cycle Low 26030842
2010 In neurons, Maf1 interacts with GABA-A receptor beta-subunit intracellular domains and co-localizes with GABA-A receptors in intracellular compartments and at the cell surface. Maf1 forms a complex with a novel protein Macoco, which also interacts with GABA-A receptors, and Macoco expression increases surface GABA-A receptor levels. Co-immunoprecipitation, subcellular localization/co-localization in neurons, Macoco overexpression assay for surface receptor quantification Molecular and cellular neurosciences Low 20417281

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Maf1 is an essential mediator of diverse signals that repress RNA polymerase III transcription. Molecular cell 190 12504022
2010 mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. Proceedings of the National Academy of Sciences of the United States of America 187 20543138
2010 mTORC1 directly phosphorylates and regulates human MAF1. Molecular and cellular biology 158 20516213
2010 Requirement of the mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells. The Journal of biological chemistry 153 20233713
2010 Molecular basis of RNA polymerase III transcription repression by Maf1. Cell 142 20887893
2014 Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLoS biology 138 24781109
2006 General repression of RNA polymerase III transcription is triggered by protein phosphatase type 2A-mediated dephosphorylation of Maf1. Molecular cell 134 16762835
2020 Maf1 Ameliorates Sepsis-Associated Encephalopathy by Suppressing the NF-kB/NLRP3 Inflammasome Signaling Pathway. Frontiers in immunology 116 33424842
2006 Dephosphorylation and genome-wide association of Maf1 with Pol III-transcribed genes during repression. Molecular cell 116 16762836
2006 Protein kinase A regulates RNA polymerase III transcription through the nuclear localization of Maf1. Proceedings of the National Academy of Sciences of the United States of America 116 17005718
2007 Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases. Molecular cell 115 17499043
2004 Two steps in Maf1-dependent repression of transcription by RNA polymerase III. The Journal of biological chemistry 94 15590667
2015 Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes & development 89 25934505
2012 Drosophila RNA polymerase III repressor Maf1 controls body size and developmental timing by modulating tRNAiMet synthesis and systemic insulin signaling. Proceedings of the National Academy of Sciences of the United States of America 89 22228302
2006 Maf1, a new player in the regulation of human RNA polymerase III transcription. PloS one 88 17205138
2007 Maf1 is involved in coupling carbon metabolism to RNA polymerase III transcription. Molecular and cellular biology 77 17785443
2014 Maf1 is a novel target of PTEN and PI3K signaling that negatively regulates oncogenesis and lipid metabolism. PLoS genetics 76 25502566
2002 The mitogen-activated protein kinase gene MAF1 is essential for the early differentiation phase of appressorium formation in Colletotrichum lagenarium. Molecular plant-microbe interactions : MPMI 74 12481999
2006 Integration of nutritional and stress signaling pathways by Maf1. Trends in biochemical sciences 71 17174096
2016 MAF1 suppresses AKT-mTOR signaling and liver cancer through activation of PTEN transcription. Hepatology (Baltimore, Md.) 68 26910647
2012 Maf1, a general negative regulator of RNA polymerase III in yeast. Biochimica et biophysica acta 68 23201230
1997 Mutation in a new gene MAF1 affects tRNA suppressor efficiency in Saccharomyces cerevisiae. Gene 63 9055829
2016 Human MAF1 targets and represses active RNA polymerase III genes by preventing recruitment rather than inducing long-term transcriptional arrest. Genome research 58 26941251
2008 Regulation of RNA polymerase III transcription by Maf1 in mammalian cells. Journal of molecular biology 55 18377933
2008 Derepression of RNA polymerase III transcription by phosphorylation and nuclear export of its negative regulator, Maf1. The Journal of biological chemistry 55 18445601
2011 Casein kinase II-mediated phosphorylation of general repressor Maf1 triggers RNA polymerase III activation. Proceedings of the National Academy of Sciences of the United States of America 54 21383183
2007 Human Maf1 negatively regulates RNA polymerase III transcription via the TFIIB family members Brf1 and Brf2. International journal of biological sciences 54 17505538
2018 Regulation of tRNA synthesis by the general transcription factors of RNA polymerase III - TFIIIB and TFIIIC, and by the MAF1 protein. Biochimica et biophysica acta. Gene regulatory mechanisms 52 29378333
1999 MAF1, a novel plant protein interacting with matrix attachment region binding protein MFP1, is located at the nuclear envelope. The Plant cell 52 10488241
2008 Facilitated recycling protects human RNA polymerase III from repression by Maf1 in vitro. The Journal of biological chemistry 47 18974046
1997 Differential expression of maf-1 and maf-2 genes in the developing rat lens. Investigative ophthalmology & visual science 47 9375588
2011 Maf1 protein, repressor of RNA polymerase III, indirectly affects tRNA processing. The Journal of biological chemistry 42 21940626
2012 PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression. The EMBO journal 38 22333918
2020 Structural basis for RNA polymerase III transcription repression by Maf1. Nature structural & molecular biology 37 32066962
2009 H2O2 activates the nuclear localization of Msn2 and Maf1 through thioredoxins in Saccharomyces cerevisiae. Eukaryotic cell 37 19581440
2016 Stress resistance and lifespan are increased in C. elegans but decreased in S. cerevisiae by mafr-1/maf1 deletion. Oncotarget 36 26934328
2013 Covalent small ubiquitin-like modifier (SUMO) modification of Maf1 protein controls RNA polymerase III-dependent transcription repression. The Journal of biological chemistry 32 23673667
2011 MAF1: a new target of mTORC1. Biochemical Society transactions 32 21428925
2018 Beyond regulation of pol III: Role of MAF1 in growth, metabolism, aging and cancer. Biochimica et biophysica acta. Gene regulatory mechanisms 31 29407795
2013 Citrus MAF1, a repressor of RNA polymerase III, binds the Xanthomonas citri canker elicitor PthA4 and suppresses citrus canker development. Plant physiology 31 23898043
2008 Regulation of RNA polymerase III transcription by Maf1 protein. Acta biochimica Polonica 30 18560610
2010 Maf1 regulation: a model of signal transduction inside the nucleus. Nucleus (Austin, Tex.) 29 21326948
2019 Maf1-dependent transcriptional regulation of tRNAs prevents genomic instability and is associated with extended lifespan. Aging cell 28 31833215
2017 Plasmodium falciparum Maf1 Confers Survival upon Amino Acid Starvation. mBio 28 28351924
2018 Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila. PLoS genetics 27 29401457
2018 Characterization of Maf1 in Arabidopsis: function under stress conditions and regulation by the TOR signaling pathway. Planta 27 30293201
2018 Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte Differentiation. Cell reports 25 30110641
2012 Maf1-mediated repression of RNA polymerase III transcription inhibits tRNA degradation via RTD pathway. RNA (New York, N.Y.) 25 22919049
2015 Emerging Roles for Maf1 beyond the Regulation of RNA Polymerase III Activity. Journal of molecular biology 24 26173035
2002 Up-regulation of tRNA biosynthesis affects translational readthrough in maf1-delta mutant of Saccharomyces cerevisiae. Current genetics 24 12491008
1994 maf1 mutation alters the subcellular localization of the Mod5 protein in yeast. Acta biochimica Polonica 24 7732762
2020 Maf1 regulates dendritic morphogenesis and influences learning and memory. Cell death & disease 23 32732865
2017 Maf1 phenotypes and cell physiology. Biochimica et biophysica acta. Gene regulatory mechanisms 23 29248739
2016 The C-Box Region of MAF1 Regulates Transcriptional Activity and Protein Stability. Journal of molecular biology 22 27986570
2000 Developmental expression of maf-1 messenger ribonucleic acids in rat kidney by in situ hybridization histochemistry. Biochemical and biophysical research communications 22 10860830
2016 Maf1, A New PTEN Target Linking RNA and Lipid Metabolism. Trends in endocrinology and metabolism: TEM 21 27296319
2015 A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells. Cell cycle (Georgetown, Tex.) 21 26030842
2020 MAF1 is a chronic repressor of RNA polymerase III transcription in the mouse. Scientific reports 19 32686713
2017 Crystal Structure and Regulation of the Citrus Pol III Repressor MAF1 by Auxin and Phosphorylation. Structure (London, England : 1993) 18 28781084
2015 MAF1 represses CDKN1A through a Pol III-dependent mechanism. eLife 18 26067234
2010 Identification and characterisation of a Maf1/Macoco protein complex that interacts with GABAA receptors in neurons. Molecular and cellular neurosciences 18 20417281
2022 Maf1 is an intrinsic suppressor against spontaneous neural repair and functional recovery after ischemic stroke. Journal of advanced research 17 36402285
2021 Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549. Aging 17 33640883
2021 Maf1 regulates intracellular lipid homeostasis in response to DNA damage response activation. Molecular biology of the cell 17 33788576
2019 Maf1 ameliorates cardiac hypertrophy by inhibiting RNA polymerase III through ERK1/2. Theranostics 17 31695767
2023 Cellular responses to long-term phosphate starvation of fission yeast: Maf1 determines fate choice between quiescence and death associated with aberrant tRNA biogenesis. Nucleic acids research 16 36794724
2020 PTEN Lipid Phosphatase Activity Enhances Dengue Virus Production through Akt/FoxO1/Maf1 Signaling. Virologica Sinica 16 33044659
2016 Maf1 is a negative regulator of transcription in Trypanosoma brucei. Molecular microbiology 15 27802583
2015 Lack of Maf1 enhances pyruvate kinase activity and fermentative metabolism while influencing lipid homeostasis in Saccharomyces cerevisiae. FEBS letters 15 26787463
2022 Maf1 mitigates sevoflurane-induced microglial inflammatory damage and attenuates microglia-mediated neurotoxicity in HT-22 cells by activating the AMPK/Nrf2 signaling. Neurotoxicology 14 35430185
2019 The RNA polymerase III repressor MAF1 is regulated by ubiquitin-dependent proteasome degradation and modulates cancer drug resistance and apoptosis. The Journal of biological chemistry 14 31645432
2015 Distinct regulation of Maf1 for lifespan extension by Protein kinase A and Sch9. Aging 14 25720796
2013 Maf1, repressor of tRNA transcription, is involved in the control of gluconeogenetic genes in Saccharomyces cerevisiae. Gene 14 23657116
2012 Recovery of RNA polymerase III transcription from the glycerol-repressed state: revisiting the role of protein kinase CK2 in Maf1 phosphoregulation. The Journal of biological chemistry 14 22810236
2010 Full repression of RNA polymerase III transcription requires interaction between two domains of its negative regulator Maf1. The Journal of biological chemistry 14 20817737
2002 The isoprenoid biosynthetic pathway in Saccharomyces cerevisiae is affected in a maf1-1 mutant with altered tRNA synthesis. FEMS yeast research 14 12702319
2021 Molecular Characterization of Paralichthys olivaceus MAF1 and Its Potential Role as an Anti-Viral Hemorrhagic Septicaemia Virus Factor in Hirame Natural Embryo Cells. International journal of molecular sciences 13 33572970
2013 MPF2-like MADS-box genes affecting expression of SOC1 and MAF1 are recruited to control flowering time. Molecular biotechnology 13 22539207
2024 Maf1 loss regulates spinogenesis and attenuates cognitive impairment in Alzheimer's disease. Brain : a journal of neurology 12 38226680
2021 Maf1 regulates axonal regeneration of retinal ganglion cells after injury. Experimental neurology 12 34902358
2008 Genetic interactions of MAF1 identify a role for Med20 in transcriptional repression of ribosomal protein genes. PLoS genetics 12 18604275
2014 Sub1 and Maf1, two effectors of RNA polymerase III, are involved in the yeast quiescence cycle. PloS one 11 25531541
2022 MAF1, a repressor of RNA polymerase III-dependent transcription, regulates bone mass. eLife 10 35611941
2021 Maf1 limits RNA polymerase III-directed transcription to preserve genomic integrity and extend lifespan. Cell cycle (Georgetown, Tex.) 9 33475456
2019 Involvement of MAF1 homolog, negative regulator of RNA polymerase III in colorectal cancer progression. International journal of oncology 9 30628658
2019 Glycolytic flux in Saccharomyces cerevisiae is dependent on RNA polymerase III and its negative regulator Maf1. The Biochemical journal 9 30885983
2015 The recombinant expression and activity detection of MAF-1 fusion protein. Scientific reports 8 26423137
2021 ΜicroRNA-122 protects against ischemic stroke by targeting Maf1. Experimental and therapeutic medicine 7 33936273
2020 The MAF1 Phosphoregulatory Region Controls MAF1 Interaction with the RNA Polymerase III C34 Subunit and Transcriptional Repression in Plants. The Plant cell 7 32641350
2005 The plant nuclear envelope protein MAF1 has an additional location at the Golgi and binds to a novel Golgi-associated coiled-coil protein. Planta 7 16231153
2016 Maf1-mediated regulation of yeast RNA polymerase III is correlated with CCA addition at the 3' end of tRNA precursors. Gene 6 27575455
2025 Feedback loop centered on MAF1 reduces blood-brain barrier damage in sepsis-associated encephalopathy. Cellular & molecular biology letters 5 39833662
2022 Impact on Arabidopsis growth and stress resistance of depleting the Maf1 repressor of RNA polymerase III. Gene 5 35017035
2024 Maf1 phosphorylation is regulated through the action of prefoldin-like Bud27 on PP4 phosphatase in Saccharomyces cerevisiae. Nucleic acids research 3 38864693
2023 Maf1 controls retinal neuron number by both RNA Pol III- and Pol II-dependent mechanisms. iScience 3 38089586
2024 Transcriptome and proteome changes triggered by overexpression of the transcriptional regulator Maf1 in the human pathogen Leishmania major. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2 39157983
2023 MAF1 is a predictive biomarker in HER2 positive breast cancer. PloS one 2 37801436
2011 cDNA cloning and sequence analysis of Musca domestica antifungal peptide-1 (MAF-1). Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases 2 21972603
2025 MAF1 inhibits hepatocarcinogenesis by fostering an immunostimulatory tumor microenvironment. Journal for immunotherapy of cancer 1 39800372
2024 Maf1 Cooperates with Progesterone Receptor to Repress RNA Polymerase III Transcription of Select tRNAs. bioRxiv : the preprint server for biology 1 39763804