Affinage

MAFA

Transcription factor MafA · UniProt Q8NHW3

Round 2 corrected
Length
353 aa
Mass
37.0 kDa
Annotated
2026-04-28
130 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Insufficient on-target evidence to synthesize a narrative — discovery timeline does not match the canonical MAFA protein.

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Mammalian MafA was identified as the RIPE3b1 factor that binds the insulin gene enhancer element RIPE3b and activates insulin gene expression. Biochemical purification from beta-cell nuclear extracts identified RIPE3b1 as a mammalian homologue of avian MafA/L-Maf, with selective expression in pancreatic beta but not alpha cells. Biochemical purification, DNA-binding assays (EMSA), luciferase reporter assays, RT-PCR Proceedings of the National Academy of Sciences of the United States of America High 12011435 12368292
2002 MafA protein and mRNA are up-regulated by glucose in beta cells, consistent with glucose-regulated binding of MafA to the RIPE3b element in beta-cell nuclear extracts. A dominant-negative form of MafA inhibited insulin promoter activity, demonstrating direct transcriptional activation. RT-PCR, EMSA, luciferase reporter assays with dominant-negative constructs The Journal of biological chemistry High 12368292
2001 MafA (quail) is phosphorylated at serines 14 and 65 within its transactivation domain by ERK2 in vitro. Mutation of these residues to alanine severely impairs transcriptional activity and abolishes MafA's ability to induce QR1 expression and neuroretina-to-lens transdifferentiation, establishing phosphorylation as essential for MafA biological activity. In vitro kinase assays with ERK2/p38/JNK/ERK5, site-directed mutagenesis (S14A, S65A), luciferase reporter assays, in ovo electroporation Molecular and cellular biology High 11416124
2005 MafA interacts directly with endogenous PDX-1 and BETA2 (NeuroD) in beta cells, forming a complex that synergistically activates the insulin gene promoter. Synergistic activation required intact MafA transactivation and DNA-binding domains. Dominant-negative and siRNA-mediated knockdown of MafA profoundly reduced insulin promoter activity in beta-cell lines. Co-immunoprecipitation (endogenous proteins), GST pull-down, luciferase reporter assays, dominant-negative constructs, siRNA knockdown, adenoviral overexpression in rat islets The Journal of biological chemistry High 15665000
2004 MafA is the only beta-cell-specific insulin gene activator and selectively induces endogenous insulin transcription in non-beta cells. MafA expression is first detected in insulin-producing cells during the second principal phase of beta-cell differentiation and is absent in Nkx6.1-null pancreata that lack second-phase beta cells, placing MafA downstream of Nkx6.1. Ectopic expression in non-beta cell lines, immunohistochemistry in Nkx6.1-/- pancreata, RT-PCR Proceedings of the National Academy of Sciences of the United States of America Medium 14973194
2005 MafA-deficient mice develop glucose intolerance and diabetes mellitus. Glucose-, arginine-, and KCl-stimulated insulin secretion are severely impaired despite normal insulin content. Transcripts for insulin 1, insulin 2, Pdx1, Beta2, and Glut-2 are diminished in MafA-deficient islets, establishing MafA as a key in vivo regulator of glucose-stimulated insulin secretion. Targeted gene knockout in mice, glucose/arginine/KCl tolerance tests, RT-PCR, islet isolation and secretion assays Molecular and cellular biology High 15923615
2005 MafA overexpression together with PDX-1 and NeuroD markedly increases insulin gene expression and protein in liver, and dramatically ameliorates glucose tolerance in streptozotocin-induced diabetic mice, demonstrating that the combination of these three transcription factors is sufficient to reprogram non-beta cells toward insulin production. Adenoviral overexpression in vivo, glucose tolerance testing in diabetic mice, RT-PCR, Western blot The Journal of biological chemistry Medium 15664997
2005 FoxO1 forms a complex with PML and SIRT1 to activate MafA (and NeuroD) expression, protecting beta cells against oxidative stress. Acetylation-defective FoxO1 mutants fail to associate with PML, are subject to ubiquitin-dependent degradation, and cannot sustain MafA expression. Hyperglycemia suppresses MafA expression in vivo, and transgenic constitutively nuclear FoxO1 prevents this suppression. Co-immunoprecipitation (FoxO1-Pml-Sirt1 complex), acetylation-defective/mimicking mutants, transgenic mice with nuclear FoxO1, in vivo MafA expression analysis Cell metabolism High 16154098
2005 MafA phosphorylation by p38 MAP kinase occurs at threonine 113, threonine 57, and serine 272 (identified by mass spectrometry and Western blot). Mutation of these residues severely impairs MafA biological activity. p38 also phosphorylates MafB and c-Maf, implicating the p38 pathway as a novel regulator of large Maf transcription factors. Western blot, mass spectrometry, in vitro kinase assay with p38, site-directed mutagenesis FEBS letters High 15963504
2006 Beta-cell-specific MafA transcription is controlled by region 3 (bp -8118 to -7750) of the mafA promoter. FoxA2, Nkx2.2, and PDX-1 were shown to specifically bind to region 3 in vivo (by ChIP) and activate MafA transcription through this region. siRNA knockdown of PDX-1 decreased mafA mRNA; MafA was absent in Nkx2.2-null pancreata. Chromatin immunoprecipitation (ChIP), luciferase reporter assays, siRNA knockdown, Nkx2.2 knockout mouse analysis, species conservation analysis Molecular and cellular biology High 16847327
2006 MafA overproduction enhances binding to the insulin promoter and increases insulin mRNA and protein, while dominant-negative MafA diminishes both. MafA regulates expression of glucokinase, Glut2, PDX1, NKX6-1, GLP1R, PCSK1, and pyruvate carboxylase in INS-1 beta cells, establishing MafA as a master regulator of genes critical for metabolism-secretion coupling. Stable INS-1 cell lines with inducible MafA overexpression or dominant-negative MafA, EMSA, RT-PCR, insulin secretion assays Diabetologia High 17149590
2006 During embryonic pancreatic development, a switch from MafB to MafA expression accompanies beta-cell differentiation. Beta-cell differentiation proceeds through a MafB+/MafA-/Ins+ intermediate cell to a MafB-/MafA+/Ins+ mature state, and MafB-to-MafA transition follows induction of high PDX-1 expression. MafA, MafB, and cMaf can each activate insulin and glucagon reporter constructs, demonstrating functional redundancy, yet display distinct cell-type-specific expression. Immunohistochemistry, co-immunofluorescence, luciferase reporter assays with ectopic Maf factor expression Developmental biology Medium 16580660
2006 Glucose induces MafA expression in beta-cell lines via the hexosamine biosynthetic pathway. Glucosamine stimulates MafA expression in the absence of high glucose; inhibition of hexosamine biosynthetic pathway abolishes glucose-induced MafA; and inhibition of O-GlcNAcase (which removes O-GlcNAc from proteins) stimulates MafA expression at low glucose, implicating O-linked glycosylation of an unknown protein as necessary for glucose-dependent MafA induction. Pharmacological inhibition of hexosamine pathway (azaserine), glucosamine supplementation, O-GlcNAcase inhibitors, RT-PCR, Western blot in INS-1 and MIN6 cells The Journal of biological chemistry Medium 17142462
2007 MafA protein stability is regulated by glucose through glycogen synthase kinase 3 (GSK3)-mediated phosphorylation at multiple N-terminal sites in beta cells. Mutational analysis and pharmacological GSK3 inhibition demonstrated that constitutive GSK3 phosphorylation is a prerequisite for rapid MafA degradation under low-glucose conditions, and glucose stabilizes MafA by modulating this pathway. In vitro kinase assays, site-directed mutagenesis of phosphorylation sites, pharmacological GSK3 inhibition in MIN6 cells, cycloheximide chase experiments Molecular and cellular biology High 17682063
2007 RIPE3b1/MafA binds directly to Area II of the pdx-1 gene 5'-flanking region (sequence blocks B4/5) with the same molecular mass and binding specificity as the insulin C1/RIPE3b1-binding protein. ChIP confirmed MafA binding to the Area II region of the endogenous pdx-1 gene, establishing that MafA directly regulates pdx-1 transcription. EMSA, molecular weight determination by gel fractionation, ChIP, Area II reporter assays with mutated binding sites The Journal of biological chemistry High 12551916
2008 MafA and MafB regulate Pdx1 transcription exclusively through Area II of the Pdx1 promoter in beta cells. In adult islets only MafA (not MafB) is bound to Area II by quantitative ChIP. In embryonic day 18.5 beta cells, both MafA and MafB are bound to Area II. A transgene driven by Pdx1 Areas I+II was severely compromised in MafB-/- mice, confirming MafB's requirement for Pdx1 expression during development. Quantitative ChIP, luciferase reporter assays, MafB knockout mouse analysis, transgenic reporter mice The Journal of biological chemistry High 18522939
2008 Phosphorylation at Ser65 of mammalian MafA governs both protein stability and transactivation potential. Ser65 phosphorylation acts as the initial degradation signal, with ubiquitinylation occurring within the C-terminus (aa 234-359). Ser65Glu (phosphomimetic) produces an unstable but transactivation-potent protein; Ser65Ala blocks degradation but reduces transactivation. Ser14 phosphorylation enhances activation without affecting turnover. Site-directed mutagenesis (S65E, S65D, S65A, S14A), cycloheximide chase, ubiquitinylation assays, luciferase reporter assays, chimeric/deletion constructs The Journal of biological chemistry High 19004825
2008 MafA is post-translationally modified by SUMO-1 and SUMO-2 at Lys32. SUMOylation increases under low glucose or hydrogen peroxide conditions. A SUMOylation-deficient mutant (K32R) shows increased transcriptional activity toward the insulin gene promoter and increased suppression of the CHOP-10 promoter. SUMOylation does not affect nuclear localization or ubiquitin-dependent degradation of MafA. SUMO modification assays, site-directed mutagenesis (K32R), luciferase reporter assays, beta-cell treatment with low glucose and H2O2, nuclear localization assays The Journal of biological chemistry High 19029092
2009 p38 MAPK is a major regulator of MafA protein stability specifically under oxidative stress. p38 MAPK inhibition enhances MafA stability under both low and high glucose; simultaneous mutation of Thr57 and Thr134 to alanine prevents p38-mediated degradation. Under oxidative stress, reduced GSK3-pathway activity (via decreased PA28γ) makes p38 MAPK the dominant degradation pathway. Pharmacological p38 inhibition (SB203580), site-directed mutagenesis (T57A, T134A double mutant), cycloheximide chase in MIN6 and mouse islets, oxidative stress experiments Molecular endocrinology High 19407223
2009 MafA expression in Pdx1+ pancreatic progenitors is detrimental to pancreatic development. Transgenic MafA expression in Pdx1+ cells reduces pancreatic mass and progenitor proliferation, at least partially through induction of cyclin kinase inhibitors p27 and p57, and disproportionately inhibits endocrine cell formation. Transgenic mouse model (MafA in Pdx1+ cells), immunohistochemistry, BrdU proliferation assay, cyclin inhibitor analysis (p27, p57) Developmental biology Medium 19576197
2009 Specific subtypes of low-threshold mechanoreceptors (LTMs) in dorsal root ganglia selectively express MafA. In Ret-deficient mice, MafA expression is reduced and central/peripheral LTM projections are compromised. In MafA mutant mice, a discrete subset of LTMs displays altered neurotrophic factor receptor expression, establishing a genetic interaction between Ret signaling and MafA in LTM specification. Immunohistochemistry, in situ hybridization, Ret knockout mouse analysis, MafA mutant mouse analysis, axon projection tracing Neuron High 20064392
2010 Phosphorylation within the MafA N-terminal transactivation domain (aa 1-72) is required for C-terminal dimerization and DNA binding. Dephosphorylation abolishes detection of MafA dimers and dramatically reduces DNA-binding ability. Analysis of MafA/MafB chimeras showed that the C-terminal dimerization region of MafA (aa 279-359) confers phosphorylation-sensitive DNA binding, whereas the homologous MafB region conveys phosphorylation-independent binding. Mass spectrometry (phosphosite identification), dephosphorylation assays, MafA/MafB chimeric protein analysis, EMSA, mutagenesis The Journal of biological chemistry High 20208071
2010 MafA regulates postnatal beta-cell function by controlling expression of genes for glucose sensing, hormone processing, vesicle formation, and insulin secretion. Microarray profiling of MafB-/- embryonic pancreata and adult MafA-null islets showed overlapping target genes, demonstrating sequential regulation: MafB controls these genes developmentally and MafA sustains their expression in adults. Microarray profiling of MafB-/- (E18.5) and pancreas-specific MafA-null adult islets, quantitative RT-PCR, in situ hybridization, immunohistochemistry Diabetes High 20627934
2010 Mafa overexpression in neonatal rat islets (via adenovirus) induces acquisition of glucose-responsive insulin secretion, increasing both the percentage of secreting beta cells and insulin secreted per cell, approaching adult levels. Mafa specifically upregulates Neurod1, Nkx6-1, glucokinase, and Glp1r mRNAs, identifying a gene expression program downstream of Mafa that drives functional maturation. Adenoviral Mafa overexpression in P2 rat islets, static insulin secretion assays, reverse haemolytic plaque assay (RHPA), quantitative RT-PCR Diabetologia High 21190012
2010 c-Jun, upregulated by reactive oxygen species under diabetic conditions, suppresses MafA expression. Adenoviral overexpression of c-Jun in MIN6 cells and isolated islets significantly decreased MafA protein and mRNA, with concomitant suppression of insulin expression. MafA overexpression restored insulin promoter activity suppressed by c-Jun, placing c-Jun upstream of MafA in a ROS-mediated pathway. Adenoviral c-Jun overexpression in MIN6 and primary islets, Western blot, immunohistochemistry in db/db mice, insulin promoter luciferase reporter Diabetes Medium 20424231
2011 ATF2 is a component of the RIPE3b1 activator complex. ATF2 alone cannot bind the C1/RIPE3b element but acquires binding capacity through complex formation with MafA. ATF2 also interacts with PDX-1 and BETA2. Co-expression of ATF2 with MafA, PDX-1, and BETA2 results in synergistic insulin promoter activation. RNAi knockdown of ATF2 in MIN6 cells reduces endogenous insulin mRNA. Co-immunoprecipitation (ATF2-MafA interaction), EMSA with ATF2/MafA complex, luciferase reporter assays, RNAi knockdown, immunohistochemistry of mouse pancreas The Journal of biological chemistry High 21278380
2011 Proteasome activator PA28γ (REGγ/PSME3) stimulates GSK3-phosphorylated MafA degradation via the 20S proteasome. PA28γ binds to phosphorylated MafA; alanine substitutions at GSK3 phosphorylation sites (Ser49, Thr53, Thr57, Ser61, Ser65) prevent PA28γ binding and confer resistance to degradation. PA28γ-mediated MafA degradation occurs through a distinct mechanism from its degradation of p21. Co-immunoprecipitation (PA28γ-MafA), site-directed mutagenesis (phosphorylation site alanine substitutions), proteasome activity assays, luciferase reporter assays, PA28γ mutant analysis (N151Y, K188D) Journal of molecular endocrinology High 21646385
2010 SUMOylation of MafA at Lys32 negatively regulates its transcriptional and oncogenic activities. A K32R SUMOylation-deficient mutant more potently transactivates crystallin and insulin gene promoters, more efficiently induces ectopic crystallin expression in developing chick embryo, and has enhanced ability to induce colony formation in DF-1 fibroblasts, demonstrating that SUMO modification restrains both transcriptional and transforming activities. Site-directed mutagenesis (K32R), luciferase reporter assays, in ovo electroporation, colony formation assay in DF-1 cells Genes to cells High 20718938
2012 miR-30d induces MafA expression by directly targeting MAP4K4 (a TNF-α-activated kinase), thereby de-repressing MafA. Overexpression of miR-30d prevents TNF-α-induced reduction in both MafA and IRS2. Overexpression of MAP4K4 suppresses MafA, and miR-30d overexpression protects against MAP4K4-mediated suppression of insulin transcription and secretion. miR-30d overexpression in beta cells, luciferase 3'UTR reporter assay (MAP4K4 as direct target), Western blot, RT-PCR, insulin secretion assays, db/db mouse islet analysis The Journal of biological chemistry Medium 22733810
2013 Thyroid hormone (triiodothyronine/T3) directly binds to the Mafa promoter region via thyroid hormone receptor, activating Mafa transcription. In vitro exposure of immature rat islets to T3 enhanced Mafa expression and glucose-responsive insulin secretion, effects abolished by dominant-negative Mafa. In vivo, neonatal T3 supplementation accelerated metabolic development; T3 inhibition delayed it. ChIP (thyroid hormone receptor binding to Mafa promoter), EMSA, luciferase reporter assay, dominant-negative Mafa in vitro, neonatal rat T3 manipulation in vivo Diabetes High 23305647
2013 p38 MAPK directly binds MafA and triggers its degradation via the ubiquitin-proteasomal pathway. Under oxidative stress (but not non-oxidative conditions), MafA degradation depends on p38-mediated phosphorylation at Thr134 (not Thr57). Expression of T134A-MafA (but not T57A-MafA) reduced oxidative stress-mediated loss of glucose-stimulated insulin secretion, independent of p38 action on protein kinase D. Co-immunoprecipitation (p38-MafA direct binding), site-directed mutagenesis (T134A, T57A), proteasome inhibitor experiments, insulin secretion assays under oxidative stress Molecular endocrinology High 23660596
2014 MafA is required for postnatal beta-cell proliferation via the prolactin signaling pathway. MafA directly transactivates the prolactin receptor (Prlr) promoter, and loss of MafA reduces Prlr and Cyclin D2 (Ccnd2) expression. Prolactin stimulation of beta cells triggers phosphorylation and translocation of Stat5B and increases nuclear Cyclin D2 pool via Prlr/Jak2 signaling, resulting in proliferation. MafA-null mice show impaired beta-cell proliferation at 4 weeks. Transcriptome analysis (MafA KO islets), Prlr promoter luciferase reporter and ChIP, prolactin stimulation of beta cells, Stat5B phosphorylation assays, BrdU proliferation in MafA-null mice PloS one High 25126749
2014 Loss of MafA reduces the beta-to-alpha cell ratio without hyperglycemia, and lineage tracing shows that most MafA-null former beta cells lose insulin expression while a minority convert to glucagon-expressing cells. MafA-null islets upregulate genes normally repressed in mature beta cells and transiently express endocrine progenitor transcription factors, hallmarks of dedifferentiation. This dedifferentiation also occurs in db/db and STZ diabetic models alongside MafB re-expression. MafA knockout mice, lineage tracing (Cre-lox), immunohistochemistry, gene expression analysis of dedifferentiation markers Diabetologia High 25500951
2014 MafA becomes functionally essential to beta cells soon after birth. Islet organization, beta-cell mass, and function are compromised by 3 weeks in Mafa-null mice and earlier in Mafa/Mafb compound mutants. Genome-wide microarray identified MafA targets including cyclin D2 (controlling beta-cell replication) and genes affecting granule docking (affecting first-phase insulin secretion), substantiated by electron microscopy. Conditional Mafa knockout mice (MafaΔpanc), compound Mafa/Mafb mutants, genome-wide microarray, electron microscopy of granule docking, metabolic assays Diabetes High 24520122
2015 MLL3 and MLL4 histone H3K4 methyltransferase complexes bind to both MafA and MAFB transcription factors in beta cells. Unbiased in-cell biochemical and mass spectrometry identified all subunits of MLL3/4 complexes as MafA-interacting proteins. MafA is associated with the ~1.5 MDa MLL3/4 complexes in size-fractionated beta-cell extracts. Knockdown of NCOA6 (core MLL3/4 subunit) reduces expression of MafA/MafB target genes. In-cell biochemistry plus mass spectrometry (unbiased pulldown), size-fractionation/Co-IP, NCOA6 siRNA knockdown, NCoA6 conditional knockout in beta cells Diabetes High 26180087
2015 HMGA1 physically interacts with PDX-1 and MafA (both in vitro by GST pulldown and in vivo by Co-IP). HMGA1 overexpression enhances the transactivating activity of PDX-1 and MafA on human and mouse insulin promoters; HMGA1 knockdown reduces this activity. High glucose stimulus increases HMGA1 binding to the insulin gene promoter (ChIP), indicating HMGA1 acts as a glucose-sensitive co-activator. GST pull-down, Co-immunoprecipitation, ChIP, luciferase reporter assays, siRNA knockdown, glucose stimulation Frontiers in endocrinology Medium 25628604
2016 MAFA directly controls ANS-mediated insulin secretion by activating transcription of nicotinic receptor genes ChrnB2 and ChrnB4, and adrenergic receptor gene Adra2A. Acetylcholine-mediated insulin secretion requires nicotinic signaling, and nicotinic receptor expression is positively correlated with insulin secretion. MAFA binding to the ChrnB4 regulatory region was demonstrated by ChIP. MafA-deficient mouse model, ChIP (MafA binding to nicotinic receptor gene loci), pharmacological nicotinic receptor blockade, insulin secretion assays, correlation with human islet data Cell reports High 26904947
2017 Mafa potentiates PDX-1's ability to induce beta-cell formation from Ngn3-positive endocrine precursors and enables PDX-1 to produce beta cells from glucagon-positive alpha cells in vivo. Transgenic conditional expression of Mafa and/or Pdx1 in Ngn3+ progenitors and glucagon+ alpha cells demonstrated that Mafa is required to permit Pdx1-driven alpha-to-beta transdifferentiation. Conditional transgenic mouse models (Mafa and/or Pdx1 in Ngn3-Cre or glucagon-Cre lineages), lineage tracing, immunohistochemistry, hormone expression analysis Diabetes High 28223284
2018 A missense MAFA mutation (p.Ser64Phe) causes familial insulinomatosis and diabetes by impairing phosphorylation within the transactivation domain, profoundly increasing MAFA protein stability under both high and low glucose conditions. The p.Ser64Phe mutation also enhances the transactivation potential of MAFA in beta-cell lines. Exome sequencing, functional studies of p.Ser64Phe in beta-cell lines (protein stability assays with cycloheximide chase, luciferase reporter for transactivation), phosphorylation analysis Proceedings of the National Academy of Sciences of the United States of America High 29339498
2018 Long noncoding RNA Meg3 epigenetically regulates MafA expression in beta cells via EZH2-mediated H3K27 trimethylation of Rad21, Smc3, and Sin3α promoters. Knockdown of Meg3 or Ezh2 upregulates Rad21, Smc3, and Sin3α, which directly repress the MafA promoter. Inhibition of Rad21, Smc3, or Sin3α individually leads to upregulated MafA expression and increased insulin production. ChIP-qPCR (EZH2/H3K27me3 at Rad21/Smc3/Sin3α promoters), RNA immunoprecipitation-qPCR (Meg3-EZH2 binding), RNAi knockdown of Meg3/Ezh2/Rad21/Smc3/Sin3α, Western blot, RT-PCR in MIN6 and mouse islets Cellular physiology and biochemistry Medium 29529600
2019 MafA directly regulates the voltage-gated Ca2+ channel subunit CaVγ4 (Cacng4) in beta cells. ChIP confirmed MafA binding to the CaVγ4 gene. CaVγ4 reduction in MafA-knockout mice suppresses L-type CaV1.2 and CaV1.3 expression, thereby suppressing voltage-gated Ca2+ entry and glucose-stimulated insulin exocytosis. ChIP (MafA binding to CaVγ4 gene), beta-cell-specific MafA knockout mice, patch-clamp electrophysiology (Ca2+ channel recordings), insulin exocytosis assays Communications biology High 30911681
2020 Kindlin-2, through its C-terminal region, directly binds to and stabilizes MafA protein in beta cells. Kindlin-2 deletion causes severe diabetes-like phenotypes; reduced MafA activity impairs insulin expression. Kindlin-2 loss also activates GSK-3β and downregulates β-catenin, reducing beta-cell proliferation and mass. Co-immunoprecipitation (Kindlin-2–MafA interaction, C-terminal domain mapping), Kindlin-2 conditional knockout mice, insulin secretion from primary human and mouse islets, Ca2+ release assays, GSK-3β/β-catenin pathway analysis Nature communications High 31980627
2021 The MAFA S64F mutation causes sex-biased beta-cell dysfunction by inducing premature aging and cellular senescence selectively in males. Male MafaS64F/+ mice display transiently higher MafA protein levels preceding glucose intolerance. MAFAS64F production in male human beta cells accelerates cellular senescence and increases senescence-associated secretory proteins compared to cells expressing MAFAWT. S64F knock-in mouse model, glucose tolerance testing, sex-stratified analysis, gene expression profiling (Ca2+ signaling, DNA damage, aging/senescence pathways), cellular senescence assays in human beta cells Cell reports High 34644565
2022 METTL3-mediated m6A methylation regulates MafA mRNA stability in beta cells. Silencing METTL3 reduces m6A levels, MafA mRNA stability, and MafA protein expression, impairing glucose-stimulated insulin secretion. Overexpression of MafA rescues the decrease in GSIS caused by METTL3 silencing, while MafA silencing blocks METTL3 overexpression-mediated rescue, placing MafA downstream of METTL3/m6A modification. m6A-seq/quantification, METTL3 siRNA knockdown and overexpression, mRNA stability assays, luciferase reporter (MafA mRNA), MafA overexpression rescue, insulin secretion assays Frontiers in endocrinology Medium 35872977
1998 Avian mafA encodes a novel large Maf protein expressed in the differentiating neuroretina. MafA binds to MARE sequences and heterodimerizes with v-Maf, MafB, Jun, and Fos (but not small Maf proteins MafF/MafK). Increased MafA expression induces sustained proliferation of postmitotic quail neuroretinal cells. cDNA cloning, EMSA (MARE binding), co-immunoprecipitation/heterodimerization assays, ectopic expression in quail neuroretinal cells Oncogene Medium 9674710
2003 MafA's strong cell-transforming ability maps to its DNA-binding domain. Chimeras of MafA and MafB correlate the strong transformation capacity of MafA with its DNA-binding domain, while weak transactivation also maps to this domain. Cell transformation and transactivation by MafA are controlled by phosphorylation of two conserved serine residues in the transactivation domain. MafA/MafB chimeric protein analysis, chicken embryo fibroblast transformation assay, luciferase reporter assays, site-directed mutagenesis of serine residues Oncogene Medium 12970735
2015 MafA directly binds to and activates MaoA and MaoB (monoamine oxidase) transcriptional control sequences in pancreatic beta cells (demonstrated by ChIP). MaoA and MaoB are expressed in mouse islet beta cells; inhibition of Mao activity reduces insulin secretion. MaoB expression is reduced in MafA-deficient mice and in type 2 diabetic mouse and human islets. ChIP (MafA binding to MaoA/MaoB gene regulatory regions), MafA-deficient mouse analysis, pharmacological Mao inhibition, insulin secretion assays Biochemical and biophysical research communications Medium 26546820
2021 PPP1R1A (protein phosphatase 1 inhibitor protein 1A) is a MafA target gene required for GLP1R-mediated amplification of glucose-stimulated insulin secretion. MafA loss or acute knockdown reduces PPP1R1A expression. PPP1R1A silencing impairs GSIS amplification, PKA-target phosphorylation, mitochondrial coupling efficiency, and expression of critical beta-cell genes including MafA, Pdx1, NeuroD1, and Pax6. MafA-deficient mouse islet transcriptomics, siRNA knockdown of PPP1R1A in INS1 cells, insulin secretion assays (GLP1-amplified GSIS), PKA substrate phosphorylation assays, mitochondrial coupling efficiency measurements Metabolism: clinical and experimental Medium 33631146

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2005 FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell metabolism 492 16154098
2005 MafA is a key regulator of glucose-stimulated insulin secretion. Molecular and cellular biology 396 15923615
2002 Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood 270 12393723
2002 Identification of beta-cell-specific insulin gene transcription factor RIPE3b1 as mammalian MafA. Proceedings of the National Academy of Sciences of the United States of America 268 12011435
2002 MafA is a glucose-regulated and pancreatic beta-cell-specific transcriptional activator for the insulin gene. The Journal of biological chemistry 250 12368292
2006 A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. Developmental biology 240 16580660
2017 PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration. Stem cell research & therapy 230 29096722
2004 The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proceedings of the National Academy of Sciences of the United States of America 225 14973194
2009 KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells. Blood 207 19406987
2010 MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes 197 20627934
2006 Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity. The Journal of experimental medicine 194 16461340
2011 MafA and MafB activity in pancreatic β cells. Trends in endocrinology and metabolism: TEM 172 21719305
2006 MAFA controls genes implicated in insulin biosynthesis and secretion. Diabetologia 167 17149590
2005 The islet beta cell-enriched MafA activator is a key regulator of insulin gene transcription. The Journal of biological chemistry 155 15665000
2009 beta-Cell-specific overexpression of glutathione peroxidase preserves intranuclear MafA and reverses diabetes in db/db mice. Endocrinology 152 19819955
2005 Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57. Journal of immunology (Baltimore, Md. : 1950) 145 15879103
1995 The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expression. Molecular endocrinology (Baltimore, Md.) 142 7491105
2010 Mafa expression enhances glucose-responsive insulin secretion in neonatal rat beta cells. Diabetologia 132 21190012
2005 Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation. Journal of virology 130 16140789
1996 Chronic exposure of betaTC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator. The Journal of clinical investigation 127 8613527
2007 PDX-1 and MafA play a crucial role in pancreatic beta-cell differentiation and maintenance of mature beta-cell function. Endocrine journal 126 17938503
2013 Thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through MAFA. Diabetes 119 23305647
2012 MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells. The Journal of biological chemistry 113 22733810
2014 MafA is critical for maintenance of the mature beta cell phenotype in mice. Diabetologia 110 25500951
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2005 A crucial role of MafA as a novel therapeutic target for diabetes. The Journal of biological chemistry 107 15664997
2014 The MafA transcription factor becomes essential to islet β-cells soon after birth. Diabetes 106 24520122
2006 FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site. Molecular and cellular biology 102 16847327
2020 Mobile health technology-supported atrial fibrillation screening and integrated care: A report from the mAFA-II trial Long-term Extension Cohort. European journal of internal medicine 98 33067121
2019 Highly differentiated cytotoxic T cells in inclusion body myositis. Brain : a journal of neurology 91 31326977
2009 Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling. Neuron 91 20064392
2012 Reprogramming of pancreatic exocrine cells towards a beta (β) cell character using Pdx1, Ngn3 and MafA. The Biochemical journal 88 22150363
2006 Analysis of CD127 and KLRG1 expression on hepatitis C virus-specific CD8+ T cells reveals the existence of different memory T-cell subsets in the peripheral blood and liver. Journal of virology 87 17079288
2016 Killer Cell Lectin-like Receptor G1 Inhibits NK Cell Function through Activation of Adenosine 5'-Monophosphate-Activated Protein Kinase. Journal of immunology (Baltimore, Md. : 1950) 86 27566818
2010 Regulation of MafA expression in pancreatic beta-cells in db/db mice with diabetes. Diabetes 85 20424231
2009 Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity 84 19604491
2001 Phosphorylation of MafA is essential for its transcriptional and biological properties. Molecular and cellular biology 84 11416124
2007 MafA regulates expression of genes important to islet beta-cell function. Molecular endocrinology (Baltimore, Md.) 83 17636040
2018 MAFA missense mutation causes familial insulinomatosis and diabetes mellitus. Proceedings of the National Academy of Sciences of the United States of America 81 29339498
2005 Relative contribution of PDX-1, MafA and E47/beta2 to the regulation of the human insulin promoter. The Biochemical journal 81 15862113
2020 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. Cell reports 79 32814053
2005 Synergistic activation of the insulin gene promoter by the beta-cell enriched transcription factors MafA, Beta2, and Pdx1. Biochimica et biophysica acta 79 15993959
2020 An atlas of immune cell exhaustion in HIV-infected individuals revealed by single-cell transcriptomics. Emerging microbes & infections 78 32954948
2023 Mobile Health-Technology-Integrated Care for Atrial Fibrillation: A Win Ratio Analysis from the mAFA-II Randomized Clinical Trial. Thrombosis and haemostasis 77 37247623
2000 NK cell expression of the killer cell lectin-like receptor G1 (KLRG1), the mouse homolog of MAFA, is modulated by MHC class I molecules. European journal of immunology 77 10741410
2010 Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset. Human immunology 75 20394788
2010 New genetic associations detected in a host response study to hepatitis B vaccine. Genes and immunity 69 20237496
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2007 Roles and regulation of transcription factor MafA in islet beta-cells. Endocrine journal 66 17785922
2013 Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves β-cell mass and function in ZDF rats. Diabetes 63 23801580
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2017 Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet α-Cells Into β-Cells In Vivo. Diabetes 55 28223284
2007 Identification of genes related to Parkinson's disease using expressed sequence tags. DNA research : an international journal for rapid publication of reports on genes and genomes 55 17213182
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1998 mafA, a novel member of the maf proto-oncogene family, displays developmental regulation and mitogenic capacity in avian neuroretina cells. Oncogene 54 9674710
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2007 Tumor-associated E-cadherin mutations affect binding to the killer cell lectin-like receptor G1 in humans. Journal of immunology (Baltimore, Md. : 1950) 53 17617594
2004 Frequent expression of the natural killer cell receptor KLRG1 in human cord blood T cells: correlation with replicative history. European journal of immunology 53 15368283
2020 KLRG1 and CD103 Expressions Define Distinct Intestinal Tissue-Resident Memory CD8 T Cell Subsets Modulated in Crohn's Disease. Frontiers in immunology 52 32477365
2018 Long Noncoding RNA Meg3 Regulates Mafa Expression in Mouse Beta Cells by Inactivating Rad21, Smc3 or Sin3α. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 52 29529600
2021 The Effects of Implementing a Mobile Health-Technology Supported Pathway on Atrial Fibrillation-Related Adverse Events Among Patients With Multimorbidity: The mAFA-II Randomized Clinical Trial. JAMA network open 51 34932104
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2006 Glucose induces MafA expression in pancreatic beta cell lines via the hexosamine biosynthetic pathway. The Journal of biological chemistry 46 17142462
2015 Cooperation between HMGA1, PDX-1, and MafA is Essential for Glucose-Induced Insulin Transcription in Pancreatic Beta Cells. Frontiers in endocrinology 42 25628604
2012 Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells. Experimental diabetes research 42 22761608
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2021 Sex-biased islet β cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males. Cell reports 41 34644565
2020 Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice. Nature communications 41 31980627
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2012 Beta cell nuclear musculoaponeurotic fibrosarcoma oncogene family A (MafA) is deficient in type 2 diabetes. Diabetologia 40 22847061
2010 Islet beta-cell-specific MafA transcription requires the 5'-flanking conserved region 3 control domain. Molecular and cellular biology 40 20584984
2008 MafA is a dedicated activator of the insulin gene in vivo. The Journal of endocrinology 40 18515495
2015 MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC. The Journal of clinical endocrinology and metabolism 39 26207953
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2009 Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells. Current medicinal chemistry 39 19689288
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2011 ATF2 interacts with beta-cell-enriched transcription factors, MafA, Pdx1, and beta2, and activates insulin gene transcription. The Journal of biological chemistry 30 21278380
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2012 Expedient chemical synthesis of 75mer DNA binding domain of MafA: an insight on its binding to insulin enhancer. Amino acids 24 22476346
2007 Islet cell differentiation in liver by combinatorial expression of transcription factors neurogenin-3, BETA2, and RIPE3b1. Biochemical and biophysical research communications 24 17239820
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2009 Definition of Mafa-A and -B haplotypes in pedigreed cynomolgus macaques (Macaca fascicularis). Immunogenetics 23 19937015
2022 The m6A Methyltransferase METTL3 Ameliorates Methylglyoxal-Induced Impairment of Insulin Secretion in Pancreatic β Cells by Regulating MafA Expression. Frontiers in endocrinology 22 35872977
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2013 Generation of functional insulin-producing cells from neonatal porcine liver-derived cells by PDX1/VP16, BETA2/NeuroD and MafA. PloS one 22 24260156
2012 Memory immune responses against pandemic (H1N1) 2009 influenza virus induced by a whole particle vaccine in cynomolgus monkeys carrying Mafa-A1*052:02. PloS one 22 22623997
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2014 Differentiation of iPSCs into insulin-producing cells via adenoviral transfection of PDX-1, NeuroD1 and MafA. Diabetes research and clinical practice 21 24794627
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