Affinage

MAF1

Repressor of RNA polymerase III transcription MAF1 homolog · UniProt Q9H063

Length
256 aa
Mass
28.8 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAF1 is a conserved phosphoprotein that acts as the central, signal-responsive repressor of RNA polymerase III transcription, coupling nutrient and stress status to the synthesis of tRNAs and other small RNAs (PMID:12504022, PMID:18377933). It was first identified in yeast as a common node through which rapamycin, DNA damage, and secretory-pathway stress converge to silence Pol III, with TFIIIB identified as the repression target (PMID:12504022). Mechanistically, MAF1 inhibits Pol III transcription in two steps—blocking de novo assembly of TFIIIB onto DNA and preventing recruitment of Pol III to preassembled TFIIIB-DNA complexes—through direct physical association with both Brf1/TFIIIB and the Pol III enzyme (PMID:15590667, PMID:17505538, PMID:17205138). Structural studies established the basis of this repression: MAF1 binds the Pol III clamp and rearranges the C82/34/31 subcomplex, sequestering the mobile C34 winged-helix domain to seal the active-center cleft, with its binding site overlapping that of TFIIIB so that closed-complex formation and reinitiation are blocked without impairing RNA synthesis itself (PMID:20887893, PMID:32066962). MAF1 activity is governed by a phosphorylation switch: under favorable growth it is phosphorylated by mTORC1 (S60/S68/S75), PKA, and CK2, which inhibits its repressive function and, in yeast, drives Msn5-dependent nuclear export (PMID:20516213, PMID:17005718, PMID:21383183, PMID:18445601); under nutrient limitation or stress, PP2A and PP4 dephosphorylate MAF1, driving its nuclear accumulation and Pol III binding (PMID:16762835, PMID:22333918). MAF1 stability is further controlled by mTOR/CUL2-dependent ubiquitin-proteasome turnover, and its association with Pol III requires SUMOylation at Lys-35 (PMID:31645432, PMID:23673667). Beyond Pol III, MAF1 modulates Pol II–driven transcription, repressing TBP and lipogenic genes (FASN, ACC1) while activating PTEN, thereby integrating into PI3K/AKT/mTOR feedback control (PMID:17499043, PMID:25502566, PMID:26910647, PMID:27986570). Through these activities MAF1 functions in vivo as a tumor suppressor and metabolic regulator, restraining anchorage-independent growth and conferring resistance to diet-induced obesity and fatty liver disease, and it additionally influences adipogenesis, cardiac hypertrophy, and neuronal plasticity (PMID:25502566, PMID:25934505, PMID:30110641, PMID:31695767, PMID:36402285).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1997 Medium

    Established MAF1 as a gene functionally linked to the tRNA biosynthetic pathway, before any molecular mechanism was known.

    Evidence Genetic screen and multicopy suppressor analysis in yeast, with RPO31/RPC160 (Pol III largest subunit) rescuing the maf1 phenotype

    PMID:9055829

    Open questions at the time
    • Did not define how Maf1 acts on Pol III
    • No biochemical interaction demonstrated
  2. 2002 High

    Defined Maf1 as a common downstream effector through which multiple stress signaling pathways repress Pol III, identifying TFIIIB as a repression target.

    Evidence Genetic epistasis across rapamycin, DNA damage, and secretory stress pathways plus biochemical repression assays in yeast

    PMID:12504022

    Open questions at the time
    • Mechanism of TFIIIB inhibition not resolved
    • No direct Maf1-Pol III contact mapped
  3. 2004 High

    Resolved the repression mechanism into two distinct biochemical steps and demonstrated direct Maf1 contacts with Brf1 and Pol III.

    Evidence In vitro transcription repression assays and co-immunoprecipitation with recombinant Maf1

    PMID:15590667

    Open questions at the time
    • Structural basis of contacts unknown
    • Non-stoichiometric mechanism not explained at the molecular level
  4. 2006 High

    Identified the kinase/phosphatase switch governing Maf1 localization and activity, placing PP2A and PKA on opposite arms of the regulatory circuit.

    Evidence ChIP-chip, genetic PP2A and PKA mutants, in vitro kinase assays, phosphosite mutants, and localization studies in yeast

    PMID:16762835 PMID:17005718

    Open questions at the time
    • Phosphatase responsible for rapid dephosphorylation not fully defined
    • Phosphosites mapped only partially in yeast
  5. 2007 High

    Extended Maf1 function to mammals and to all three nuclear polymerases, revealing Pol II target genes (TBP) and growth-suppressive activity.

    Evidence Knockdown/overexpression in glioblastoma lines, ChIP, and reporter assays for Pol I/II/III and the TBP promoter

    PMID:17205138 PMID:17499043 PMID:17505538

    Open questions at the time
    • Whether Pol I/II repression is direct or indirect
    • Physiological significance of multi-polymerase repression unclear
  6. 2008 High

    Demonstrated that mammalian Maf1 directly engages Pol III and TFIIIB and represses Pol III at chromosomal templates, while in yeast phosphorylation drives Msn5-dependent nuclear export.

    Evidence Co-IP, in vitro transcription, ChIP, Maf1 knockout cells, and genetic Msn5 deletion plus localization imaging

    PMID:18377933 PMID:18445601 PMID:18974046

    Open questions at the time
    • Mammalian export pathway differs and was not resolved here
    • Why recombinant Maf1 cannot block facilitated recycling in vitro
  7. 2010 High

    Established mTORC1 as the direct upstream kinase and resolved the structural basis of repression, unifying signaling and mechanism.

    Evidence In vitro mTORC1 kinase assays with S60/S68/S75 mutagenesis, phosphoproteomics, proximity ligation assays, X-ray crystallography and cryo-EM of Pol III-Maf1 complexes

    PMID:20233713 PMID:20516213 PMID:20543138 PMID:20817737 PMID:20887893

    Open questions at the time
    • How dephosphorylation translates structurally into Pol III binding
    • Species difference in nuclear export not mechanistically reconciled
  8. 2011 High

    Placed CK2 as an activating kinase that releases Maf1 from Pol III to restore transcription on return to growth.

    Evidence In vitro CK2 kinase assays on recombinant Maf1, ChIP, and tRNA synthesis assays in maf1Δ cells

    PMID:21383183

    Open questions at the time
    • CK2 phosphosites not mapped
    • Interplay with mTORC1/PKA phosphorylation not resolved
  9. 2012 High

    Identified PP4 as the principal Maf1 phosphatase mediating rapid stress-induced dephosphorylation, and clarified that maf1Δ tRNA processing defects are indirect.

    Evidence In vitro dephosphorylation with purified PP4, co-precipitation, genetic PP4 subunit deletions, and pre-tRNA accumulation analysis in yeast

    PMID:21940626 PMID:22333918

    Open questions at the time
    • Coordination between PP2A and PP4 not fully defined
    • Mammalian counterpart of PP4 activity not established
  10. 2014 High

    Integrated MAF1 into PTEN/PI3K/AKT tumor-suppressor signaling and lipogenic gene control, defining a Pol II–dependent metabolic role.

    Evidence PTEN KO mouse models, ChIP at the FASN promoter, reporter assays, and xenograft tumor models

    PMID:25502566

    Open questions at the time
    • Direct vs indirect FASN repression mechanism
    • Relationship between Pol III and Pol II targets not unified
  11. 2015 High

    Demonstrated SUMOylation at K35 as a modification required for Maf1-Pol III association and identified MAF1 as a whole-body metabolic regulator in mice.

    Evidence SUMO modification assays with K35R mutagenesis, ChIP, and metabolic phenotyping of whole-body Maf1 knockout mice with tRNA precursor/mature ratio measurements

    PMID:23673667 PMID:25934505 PMID:26067234

    Open questions at the time
    • How SUMOylation mechanistically promotes Pol III binding
    • Source of futile tRNA cycling not pinpointed
  12. 2016 Medium

    Defined the C-box autoregulatory region, genome-wide selectivity of Pol III targeting, and a paradoxical PTEN-activator role.

    Evidence C-box deletion/mutation analysis, genome-wide Pol III/MAF1 ChIP-seq with EU-labeling of nascent RNAs, and PTEN promoter acetylation/reporter assays

    PMID:26910647 PMID:26941251 PMID:27986570

    Open questions at the time
    • Molecular switch between repressor and activator functions unknown
    • MAF1L/MAF1S stoichiometry regulation incompletely defined
  13. 2019 Medium

    Established CUL2-mediated, phosphorylation-coupled proteasomal turnover as a layer of MAF1 abundance control and linked MAF1 to ERK-dependent cardiac hypertrophy.

    Evidence Ubiquitination and stability assays with CUL2 knockdown and S75 mutants; Maf1 KO/overexpression mice with ERK1/2 co-IP and U0126 inhibition

    PMID:31645432 PMID:31695767

    Open questions at the time
    • CUL2 substrate-recognition module not identified
    • Direct vs indirect Maf1-ERK1/2 interaction needs reciprocal validation
  14. 2020 High

    Provided high-resolution structural confirmation of active-site sealing and broadened MAF1 to chronic Pol III repression in vivo and to inflammatory (NLRP3) transcriptional control.

    Evidence 3.3-Å cryo-EM of yeast Maf1-Pol III; ChIP-seq across fasting/refeeding in Maf1 KO mouse liver; ChIP and reporter assays at the NLRP3 promoter

    PMID:32066962 PMID:32686713 PMID:33424842

    Open questions at the time
    • Generality of NLRP3 promoter binding across cell types
    • Link between chronic Pol III repression and translational output incompletely defined
  15. 2022 Medium

    Expanded MAF1 into neuronal gene regulation, showing it represses both Pol III genes and CREB-associated plasticity genes downstream of mTOR.

    Evidence AAV knockdown, CUT&TAG-seq promoter mapping, and stroke model with neurite/spine morphology analysis in mouse cortical neurons

    PMID:36402285

    Open questions at the time
    • Mechanism of MAF1 recruitment to Pol II/CREB promoters unknown
    • Direct vs indirect effects on plasticity genes
  16. 2025 Medium

    Showed nuclear receptor cooperation, with progesterone receptor recruiting Maf1 to repress selected tRNA genes in a ligand-dependent manner.

    Evidence ChIP-seq for PR/Pol III/Brf1/Maf1, nascent tRNA analysis, co-IP, and Maf1 knockdown

    PMID:41206048

    Open questions at the time
    • Whether PR-Maf1 interaction is direct
    • Selectivity determinants for the ~50% of targeted tRNA genes

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MAF1 mechanistically toggles between repressing Pol III and Pol II targets and activating PTEN, and how it is recruited to specific Pol II promoters, remains unresolved.
  • No structural model for MAF1 at Pol II promoters
  • Recruitment determinants for Pol II/CREB/PR targets unknown
  • Switch between repressor and activator modes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 3 R-HSA-8953854 Metabolism of RNA 3
Partners
BRF1BRF2CUL2ERK1/2MSN5PCNAPOLR3ATBP

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Maf1 is a common component of multiple signaling pathways in S. cerevisiae that repress RNA Pol III transcription. Signaling pathways activated by rapamycin (nutrient limitation), DNA damage, and secretory pathway defects all require Maf1 for Pol III transcriptional repression. TFIIIB was identified as a target of Maf1-dependent repression, with a defect in TFIIIB-DNA complex assembly under repressing conditions. Genetic epistasis, biochemical repression assays in yeast Molecular cell High 12504022
1997 MAF1 was identified as a novel yeast gene whose mutation causes antisuppression of a tRNA suppressor and temperature-sensitive respiratory growth. A fragment of RPO31/RPC160 (largest subunit of RNA Pol III) was cloned as a multicopy suppressor of maf1-1, suggesting Maf1 acts in the tRNA biosynthetic pathway via Pol III. Genetic screen, complementation cloning, multicopy suppressor analysis Gene Medium 9055829
2004 Maf1-dependent repression of Pol III transcription involves two steps: (1) inhibition of de novo TFIIIB assembly onto DNA and (2) inhibition of Pol III recruitment to preassembled TFIIIB-DNA complexes. Brf1 (a TFIIIB subunit) was identified as a target of repression. Maf1-Brf1 and Maf1-Pol III interactions were demonstrated by co-immunoprecipitation and implicated in these inhibitory steps. Maf1 functions via a non-stoichiometric mechanism. In vitro transcription repression assays, co-immunoprecipitation with recombinant Maf1 The Journal of biological chemistry High 15590667
2006 PP2A (protein phosphatase type 2A) is required for rapamycin-induced Maf1 dephosphorylation, nuclear accumulation, and Pol III repression. Maf1 interacts with Pol III (largest subunit C160 identified as target) in a dephosphorylated state. Under repressing conditions, Maf1 dephosphorylation by PP2A drives nuclear accumulation and increased Pol III-Maf1 interaction. Mutations in PP2A catalytic subunit genes prevented these events. ChIP-chip genome-wide analysis, phosphorylation state analysis, genetic mutation of PP2A subunits, co-immunoprecipitation Molecular cell High 16762835
2006 Protein kinase A (PKA) phosphorylates Maf1 in vitro at PKA consensus sites. PKA activity negatively regulates Maf1 function: strains with unregulated high PKA activity block Pol III repression, while strains lacking all PKA activity are hyperrepressible. PKA inhibits Maf1 nuclear import via the N-terminal nuclear localization sequence, thereby preventing Pol III repression. In vitro kinase assay, differential in vivo phosphorylation analysis, genetic strains with altered PKA activity, phosphosite mutant analysis, nuclear localization studies 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, and also represses TBP (TATA binding protein) transcription (Pol II-dependent) by targeting an Elk-1-binding site in the TBP promoter. Maf1 occupancy at this site is reciprocal with Elk-1 occupancy. Maf1 overexpression suppresses anchorage-independent growth. Expression knockdown/overexpression in glioblastoma lines, chromatin immunoprecipitation, reporter assays Molecular cell High 17499043
2007 Human Maf1 represses Pol III transcription via TFIIIB, specifically through the TFIIB family members Brf1 and Brf2. In vivo Pol III luciferase assay, co-immunoprecipitation International journal of biological sciences Medium 17505538
2007 Maf1 regulation of Pol III transcription is important for the switch between fermentation and respiration in yeast. Under respiratory conditions, Maf1 is dephosphorylated and imported into the nucleus; glucose addition induces Maf1 phosphorylation and cytoplasmic relocation. Absence of Maf1 impairs viability on nonfermentable carbon sources and differentially regulates levels of different tRNAs. Phosphorylation state analysis, subcellular localization, genetic suppressor studies, tRNA level measurements Molecular and cellular biology Medium 17785443
2008 Mammalian Maf1 interacts with Pol III and TFIIIB in mouse and human cells (co-immunoprecipitation). Maf1 represses Pol III transcription in vitro and in transfected fibroblasts. Maf1 is phosphorylated in a serum-sensitive manner in vivo. Genetic deletion of Maf1 elevates Pol III transcript expression. Maf1 is detected at chromosomal Pol III templates. Co-immunoprecipitation, in vitro transcription, fibroblast transfection, ChIP, Maf1 knockout cells Journal of molecular biology High 18377933
2008 Phosphorylation of Maf1 by nuclear kinases drives its nuclear export via the Msn5 exportin carrier. Maf1 physically interacts with Msn5 (demonstrated by co-immunoprecipitation). In msn5Δ cells, Maf1 remains in the nucleus upon glucose addition despite normal phosphorylation, demonstrating that phosphorylation acts both directly (decreasing Pol III repression) and indirectly (stimulating Msn5-mediated nuclear export). Co-immunoprecipitation, subcellular localization imaging, genetic deletion of Msn5, phosphorylation analysis in Maf1 phosphosite mutants The Journal of biological chemistry High 18445601
2008 Human Maf1 can inhibit TFIIIB and Pol III recruitment to immobilized templates in vitro. However, Pol III bound to preinitiation complexes or in elongation complexes is protected from Maf1 repression and can undergo facilitated recycling (multiple rounds of reinitiation). Recombinant Maf1 is unable to inhibit facilitated recycling, suggesting additional biochemical steps are needed for rapid repression in vivo. Immobilized template in vitro transcription assay, recombinant human Maf1 The Journal of biological chemistry High 18974046
2006 Human Maf1 co-immunoprecipitates with Pol III and associates in vitro with two Pol III subunits: the largest subunit RPC1 and the alpha-like subunit RPAC2. Maf1 represses Pol III transcription in vitro and in vivo, and is required for maximal Pol III repression after MMS or rapamycin treatment, both of which lead to Maf1 dephosphorylation. Co-immunoprecipitation, in vitro binding assay with Pol III subunits, in vitro and in vivo transcription repression assays PloS one High 17205138
2009 H2O2-induced nuclear accumulation of Maf1 in S. cerevisiae requires the cytoplasmic thioredoxins Trx1 and Trx2. PP2A phosphatase activity is essential for H2O2-induced Maf1 dephosphorylation and nuclear accumulation. Unlike other stresses, H2O2-induced Maf1 nuclear accumulation does not correlate with downregulation of PKA kinase activity. Subcellular localization analysis, genetic deletion of TRX1/TRX2 and PP2A subunits, phosphorylation state analysis Eukaryotic cell Medium 19581440
2010 Crystal structure of Maf1 and cryo-EM structures of Pol III, active Pol III-DNA-RNA complex, and repressive Pol III-Maf1 complex were determined. Maf1 binds the Pol III clamp and rearranges the C82/34/31 subcomplex at the rim of the active center cleft, impairing recruitment of Pol III to promoter DNA with Brf1 and TBP and preventing closed complex formation. Maf1 does not impair binding of a DNA-RNA scaffold or RNA synthesis, explaining specific repression of initiation. X-ray crystallography, cryo-electron microscopy, functional complex reconstitution Cell High 20887893
2010 mTORC1 directly phosphorylates human MAF1 on 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 by mTORC1 inhibits MAF1's repression activity. In vitro kinase assay with mTORC1, phosphorylation site mutagenesis, rapamycin/Torin1 treatment, MAF1 knockdown/knockout Molecular and cellular biology High 20516213
2010 mTOR associates with TFIIIC via a TOR signaling motif in TFIIIC, is recruited to tRNA and 5S rRNA genes, and phosphorylates Maf1 at Ser-75 in a mTOR-dependent manner both in vitro and in vivo. mTOR-Maf1 and mTOR-TFIIIC interactions were confirmed by proximity ligation assays in nuclei. In contrast to yeast, no nuclear export of Maf1 was found in HeLa cells in response to mTOR signaling. In vitro phosphorylation assay, proximity ligation assay, ChIP, knockdown experiments Proceedings of the National Academy of Sciences of the United States of America High 20543138
2010 Maf1 Ser-75 phosphorylation by mTOR (identified by quantitative phosphoproteomics) controls its nuclear accumulation and Pol III repression in cancer cells. mTOR inhibition leads to rapid Maf1 dephosphorylation, nuclear accumulation, and reduced pre-tRNA levels. Maf1-S75A and Maf1-4A (S75A+S60A+T64A+S68A) mutants progressively enhance basal tRNA repression. mTOR inhibition increases Maf1 occupancy at Pol III genes with concomitant loss of Pol III and Brf1 binding. Quantitative phosphoproteomics, siRNA knockdown, phosphosite mutant analysis, ChIP, pre-tRNA measurements The Journal of biological chemistry High 20233713
2010 Two conserved domains of human Maf1 are resistant to mild proteolysis and interact with each other (demonstrated by pull-down and size-exclusion chromatography). Comparable domains of yeast Maf1 interact in two-hybrid assay. Integrity of both domains and their direct interaction are necessary for Maf1 dephosphorylation and subsequent Pol III transcription inhibition on nonfermentable carbon sources. Limited proteolysis, pull-down assay, size-exclusion chromatography, two-hybrid assay, functional transcription assays The Journal of biological chemistry Medium 20817737
2011 Casein kinase II (CK2) phosphorylates Maf1 directly: both recombinant human and yeast CK2 phosphorylate purified human or yeast Maf1 in vitro. CK2 activity is required for efficient Pol III transcription by releasing Maf1 from Pol III at tRNA genes upon return to favorable growth conditions. In maf1Δ cells, CK2 inhibition has no effect on tRNA synthesis, confirming CK2 activates Pol III via Maf1. In vitro kinase assay with recombinant CK2 and Maf1, ChIP, tRNA synthesis assay in maf1Δ cells Proceedings of the National Academy of Sciences of the United States of America High 21383183
2012 Protein phosphatase 4 (PP4) complex (with catalytic subunit Pph3, scaffold Psy2, regulatory subunits Rrd1 and Tip41) is the main Maf1 phosphatase in yeast. PP4 co-precipitates with Maf1, and purified PP4 dephosphorylates Maf1 in vitro. PP4 mediates rapid Maf1 dephosphorylation in response to diverse stresses, Maf1 nuclear localization, and rapid Pol III repression. In vitro dephosphorylation assay with purified PP4, co-precipitation, genetic deletion of PP4 subunits, localization and transcription assays The EMBO journal High 22333918
2013 Maf1 is SUMOylated by SUMO1 and SUMO2, with Lys-35 as the major SUMOylation site. The deSUMOylase SENP1 controls Maf1-K35 SUMOylation. SUMOylation is required for Maf1 to repress Pol III transcription and suppress colony growth. Maf1-K35R (non-SUMOylatable) is defective in associating with Pol III, impairing its recruitment to tRNA gene promoters and its ability to dissociate Pol III from these promoters. SUMOylation does not alter Maf1 subcellular localization and is unaffected by mTOR/rapamycin. SUMO modification assay, site-directed mutagenesis (K35R), co-immunoprecipitation, ChIP, colony growth assay The Journal of biological chemistry High 23673667
2014 Maf1 is a key downstream target of PTEN that drives PTEN's tumor suppressor and metabolic functions. PTEN-mediated changes in Maf1 expression are mediated through PI3K/AKT/FoxO1 signaling. Maf1 occupies the FASN promoter and opposes SREBP1c-mediated transcription activation of lipogenic enzymes. Maf1 reduces anchorage-independent growth and tumor formation in mice. PTEN KO mouse models, human cancer samples, ChIP, reporter assays, xenograft tumor models, lipid accumulation assays PLoS genetics High 25502566
2015 Whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Precursor tRNA synthesis is increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Maf1 knockout also leads to elevated futile cycling of hepatic lipids and increased NAD+ levels in muscle. Whole-body Maf1 knockout mice, metabolic phenotyping, tRNA precursor/mature ratio measurements, metabolite profiling Genes & development High 25934505
2015 MAF1 knockdown induces CDKN1A transcription concurrently with Pol III recruitment to the CDKN1A locus. Simultaneous knockdown of MAF1 with Pol III or BRF1 diminishes CDKN1A activation and chromatin looping, indicating that Pol III recruitment is required for this Pol II-mediated transcription and looping. ChIP shows enhanced binding of Pol III, BRF1, CFP1, p300, PCAF, TBP, and POLR2E at the CDKN1A promoter upon MAF1 knockdown. siRNA knockdown, ChIP analysis, chromatin looping assay, transcription measurements eLife Medium 26067234
2016 MAF1 binds the PTEN promoter, enhancing PTEN promoter acetylation and transcriptional activity (acting as a transcriptional activator for PTEN, contrary to its canonical repressor function). MAF1 downregulation leads to decreased PTEN expression and paradoxical activation of AKT-mTOR signaling. ChIP, promoter acetylation assay, luciferase reporter, MAF1 knockdown/overexpression in HCC cells and mouse models Hepatology (Baltimore, Md.) Medium 26910647
2016 Human MAF1 targets and represses active Pol III genes by preventing Pol III recruitment rather than inducing long-term transcriptional arrest. MAF1 selectively localizes at Pol III loci even under serum-replete conditions and increasingly targets transcribing Pol III in response to serum starvation. Pol III occupancy closely reflects ongoing transcription (validated by EU-labeling of nascent small RNAs). Genome-wide Pol III binding (ChIP-seq), EU-labeling with high-throughput sequencing of nascent small RNAs, MAF1 ChIP Genome research High 26941251
2016 The MAF1 C-box region negatively regulates MAF1 activity. C-box deletion in human MAF1 leads to increased nuclear localization and enhanced repression of ACC1 and FASN, but impaired repression of Pol III targets. C-box mutations render MAF1 insensitive to rapamycin. The YSY motif in the C-box controls MAF1 species stoichiometry (MAF1L and MAF1S) and proteasome-dependent turnover of nuclear MAF1. C-box deletion/mutation analysis in C. elegans and human cells, nuclear localization imaging, proteasome inhibition, rapamycin treatment, transcription assays Journal of molecular biology Medium 27986570
2018 Ras/ERK signaling promotes Pol III-mediated tRNA synthesis in Drosophila by phosphorylating Maf1, inhibiting its nuclear localization and function as a Pol III repressor. ERK activation promotes tRNA synthesis both in vivo and in cultured S2 cells. Myc is required but not sufficient for Ras-mediated tRNA stimulation; instead, inhibition of Maf1 nuclear localization is the key mechanism. In vivo Drosophila genetic experiments, cultured S2 cells, ERK/Ras pathway activation/inhibition, Pol III reporter assays, Maf1 localization imaging PLoS genetics Medium 29401457
2018 Maf1 promotes induction of mouse embryonic stem cells into mesoderm and promotes adipocyte differentiation. Reduced Maf1 expression impairs adipogenesis, while ectopic Maf1 expression in Maf1-deficient cells enhances differentiation. RNA Pol III repression promotes adipogenesis; Pol III-mediated transcription positively regulates lncRNA H19 and Wnt6 (adipogenesis inhibitors). Maf1 KO/overexpression in mESCs and preadipocytes, Brf1 knockdown, chemical Pol III inhibition, RNA-seq Cell reports Medium 30110641
2019 MAF1 is regulated by ubiquitin-dependent proteasome degradation. TORC1-mediated phosphorylation at Ser-75 enhances MAF1 ubiquitination. The E3 ubiquitin ligase CUL2 critically regulates MAF1 ubiquitination and controls its stability and subsequent Pol III-dependent transcription. Modulating CUL2 or MAF1 expression alters actin cytoskeleton reorganization and sensitivity to doxorubicin-induced apoptosis. Ubiquitination assay, proteasome inhibition, CUL2 knockdown, phosphosite mutant analysis, cell viability/apoptosis assays The Journal of biological chemistry Medium 31645432
2019 Maf1 directly binds ERK1/2 (demonstrated by immunoprecipitation) and inhibits Pol III transcription via ERK1/2 signaling suppression to attenuate cardiac hypertrophy. Maf1 KO mice exhibit exacerbated cardiac hypertrophy after pressure overload; Maf1 overexpression ameliorates hypertrophy. ERK1/2 inhibition by U0126 suppresses Maf1-knockdown-promoted cardiac hypertrophy with concomitant Pol III repression. Maf1 KO mice, adenoviral overexpression, co-immunoprecipitation with ERK1/2, ERK inhibitor U0126, cardiac phenotyping Theranostics Medium 31695767
2020 Cryo-EM structure of yeast Maf1 bound to Pol III at 3.3-Å resolution. Maf1 sequesters Pol III elements involved in transcription initiation and binds the mobile C34 winged helix 2 domain, sealing off the active site. The Maf1 binding site overlaps with that of TFIIIB in the preinitiation complex. Cryo-electron microscopy at 3.3-Å resolution Nature structural & molecular biology High 32066962
2020 Maf1 and p65 (NF-κB) directly bind to the NLRP3 gene promoter region and competitively regulate NLRP3 function in inflammation. Maf1 downregulates NF-κB/p65-induced NLRP3 inflammasome activation and pro-inflammatory cytokine expression, suppressing LPS-induced BBB disruption. ChIP at NLRP3 promoter, reporter assay, overexpression/knockdown, in vitro and in vivo LPS models Frontiers in immunology Medium 33424842
2020 MAF1 functions as a chronic repressor of active Pol III loci in the mouse liver. In Maf1-/- mice, Pol III occupancy is higher than wild-type at the vast majority of active loci in both fasted and refed conditions, and specific precursor tRNA levels are elevated in multiple tissues. MAF1 has a modest effect on global translation via reduced mRNA levels and translation efficiencies for several ribosomal proteins. ChIP-seq, precursor tRNA measurements, polysome profiling, fasting-refeeding paradigm in Maf1 KO mice Scientific reports High 32686713
2021 Maf1 regulates intracellular lipid homeostasis in C. elegans in response to DNA damage via the DDR pathway. UV-induced lipid accumulation requires mafr-1, the apical kinases atm-1 and atl-1 (DDR kinases). Genetic ablation of mafr-1 alone activates the DDR, including increased lipid accumulation, phosphorylation of ATM/ATR target proteins, and expression of Bcl-2 homolog genes. C. elegans genetic deletion, UV exposure, lipid accumulation quantification, DDR marker analysis Molecular biology of the cell Medium 33788576
2021 In response to ionizing radiation (IR), Maf1 is inhibited by Akt-dependent re-phosphorylation, which activates the mitochondrial unfolded protein response (UPRmt) through ATF5. Rapamycin suppresses IR-induced Maf1 re-phosphorylation and UPRmt activation in A549 cells, increasing radio-sensitivity. Maf1 overexpression suppresses ethidium bromide-induced UPRmt and enhances IR-mediated cytotoxicity. Maf1 knockdown/overexpression, rapamycin treatment, IR exposure, UPRmt marker analysis, mitochondrial membrane potential measurement Aging Medium 33640883
2022 Maf1 mediates mTOR signaling to regulate Pol III-dependent rRNA and tRNA transcription in mouse cortical neurons. mTOR regulates neuronal Maf1 phosphorylation and subcellular localization. Maf1 knockdown increases Pol III transcription, neurite outgrowth, and dendritic spine formation. Maf1 interacts with promoters of CREB-associated genes (in addition to Pol III genes), repressing plasticity-related genes in neurons. AAV-mediated Maf1 knockdown, CUT&TAG-seq genome-wide promoter mapping, photothrombotic stroke model, neurite/spine morphology analysis Journal of advanced research Medium 36402285
2024 Bud27 (a prefoldin-like protein) regulates Maf1 phosphorylation state and nuclear localization through its association with the PP4 phosphatase complex. Bud27 associates with PP4 in vivo, and loss of Bud27 decreases PP4-Maf1 interaction, reduces Maf1 dephosphorylation, and impairs Maf1 nuclear entry. Co-immunoprecipitation of Bud27 with PP4, Maf1 phosphorylation state analysis, nuclear localization studies in bud27Δ cells Nucleic acids research Medium 38864693
2024 Maf1 regulates NMDAR1 (encoded by Grin1) expression by binding to the Grin1 promoter region, thereby regulating calcium homeostasis and synaptic remodeling in neurons. Conditional Maf1 knockout in a transgenic Alzheimer's disease mouse model restored learning and memory function. ChIP-PCR at Grin1 promoter, luciferase reporter assay, conditional Maf1 KO in transgenic AD mice, calcium imaging, synaptic morphology analysis Brain : a journal of neurology Medium 38226680
2025 Maf1 cooperates with progesterone receptor (PR) to repress Pol III transcription of select tRNA genes in a progestin-dependent manner. Upon progestin treatment, PR localizes to ~50% of POLR3A-occupied tRNA genes, with Maf1 co-recruited at many of these sites. PR and Maf1 interact in a progestin-dependent manner (co-immunoprecipitation). Maf1 knockdown attenuates progestin-induced tRNA transcription downregulation. ChIP-seq for PR, Pol III subunits, Brf1, and Maf1; nascent tRNA transcription analysis; co-immunoprecipitation; Maf1 knockdown Nucleic acids research Medium 41206048
2012 Maf1 protein indirectly affects tRNA processing in yeast. The maf1Δ strain accumulates primary transcripts and intron-containing pre-tRNAs due to saturation of the tRNA processing machinery by increased primary transcripts rather than a direct role of Maf1 in maturation. Saturation of the tRNA exportin Los1 is one reason for pre-tRNA accumulation in maf1Δ cells. Pre-tRNA accumulation analysis, transcription inhibition rescue experiments, Los1 loss-of-function analysis in maf1Δ The Journal of biological chemistry Medium 21940626
2010 MAF1 is a novel PCNA-interacting protein in human cells, validated by co-immunoprecipitation from human cell extracts and interaction analysis using recombinant proteins. Bimolecular fluorescence complementation screen, co-immunoprecipitation from human cell extracts, recombinant protein interaction assay Cell cycle (Georgetown, Tex.) Low 26030842
2010 Maf1 interacts with GABA-A receptor beta-subunit intracellular domains in neurons. Maf1 co-localizes with GABA-A receptors in intracellular compartments and at the cell surface in neurons. Maf1 interacts with a novel coiled-coil protein Macoco, which also interacts with GABA-A receptors. Expressing Macoco in neurons increases surface GABA-A receptor levels. Co-immunoprecipitation with GABA-A receptor subunits, co-localization by immunofluorescence, Macoco overexpression in neurons 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 160 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 143 20887893
2014 Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLoS biology 141 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 118 33424842
2007 Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases. Molecular cell 116 17499043
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
2004 Two steps in Maf1-dependent repression of transcription by RNA polymerase III. The Journal of biological chemistry 94 15590667
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 90 22228302
2015 Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes & development 89 25934505
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.) 69 26910647
2012 Maf1, a general negative regulator of RNA polymerase III in yeast. Biochimica et biophysica acta 69 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
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 54 29378333
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
1999 MAF1, a novel plant protein interacting with matrix attachment region binding protein MFP1, is located at the nuclear envelope. The Plant cell 53 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
2020 Structural basis for RNA polymerase III transcription repression by Maf1. Nature structural & molecular biology 38 32066962
2012 PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression. The EMBO journal 38 22333918
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
2017 Plasmodium falciparum Maf1 Confers Survival upon Amino Acid Starvation. mBio 29 28351924
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
2018 Ras/ERK-signalling promotes tRNA synthesis and growth via the RNA polymerase III repressor Maf1 in Drosophila. PLoS genetics 27 29401457
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 Maf1, A New PTEN Target Linking RNA and Lipid Metabolism. Trends in endocrinology and metabolism: TEM 22 27296319
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
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
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 18 36794724
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
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.) 10 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
2025 Feedback loop centered on MAF1 reduces blood-brain barrier damage in sepsis-associated encephalopathy. Cellular & molecular biology letters 6 39833662
2016 Maf1-mediated regulation of yeast RNA polymerase III is correlated with CCA addition at the 3' end of tRNA precursors. Gene 6 27575455
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
2023 Contrasting effects of whole-body and hepatocyte-specific deletion of the RNA polymerase III repressor Maf1 in the mouse. Frontiers in molecular biosciences 1 38143800
2026 Toxoplasma gondii effector MAF1 blocks mouse AIM2 inflammasome activation by inhibiting mtDNA release. Journal of immunology (Baltimore, Md. : 1950) 0 41764738
2025 Maf1 cooperates with progesterone receptor to repress RNA polymerase III transcription of select tRNAs. Nucleic acids research 0 41206048

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