Affinage

MITF

Microphthalmia-associated transcription factor · UniProt O75030

Length
526 aa
Mass
58.8 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MITF is a basic-helix-loop-helix leucine-zipper (bHLH-Zip) transcription factor that acts as a master regulator of the melanocyte lineage and a broader rheostat of cell state, capable of instructively converting fibroblasts into pigment-producing cells with melanocyte morphology and marker expression (PMID:9170159). It binds E-box/CLEAR-box consensus sequences as a homodimer—the palindromic CLEAR-box inducing symmetric dimer binding (PMID:30705290)—to directly activate melanocyte differentiation genes including SILV/PMEL17 and MLANA (PMID:12819038), the receptor c-Met (PMID:16455654), and the transporter ABCB5 in cooperation with β-catenin (PMID:31595650). MITF couples differentiation to cell-cycle exit by directly activating the CDK inhibitors p21(Cip1)/CDKN1A (potentiated by Rb1) and p16(INK4A), driving Rb hypophosphorylation and G1 arrest (PMID:15716956, PMID:15623583), and controls invasiveness by activating the formin DIAPH1/Dia1 to remodel the actin cytoskeleton and limit ROCK-dependent invasion (PMID:17182868) while directly repressing ECM-remodeling and EMT genes such as CDH2 (PMID:33438577), consistent with a reversible rheostat model of melanoma phenotype switching. Beyond pigment cells, MITF directs lysosomal/autophagosomal biogenesis through CLEAR-box targets and sustains starvation-induced autophagy via a MITF-MIR211-RICTOR feed-forward loop (PMID:30705290, PMID:30290719), promotes endolysosomal sequestration of the Wnt destruction complex to amplify Wnt signaling (PMID:25605940), and functions downstream of M-CSF/RANKL signaling in osteoclast differentiation by cooperating with PU.1, NFATc1 and SWI/SNF (PMID:11684011, PMID:17403683). MITF activity is governed by an extensive post-translational and transcriptional control network: SUMOylation at a conserved consensus site tunes transcriptional synergy at multi-site promoters, and the germline E318K substitution disrupts this modification to produce a gain-of-function, globally hyper-occupant MITF (PMID:15507434, PMID:22012259, PMID:22080950); BRAF/MAPK priming followed by GSK3 phosphorylation activates a hydrophobic nuclear export signal (PMID:30150413); AKT phosphorylation at S510 switches target specificity from tyrosinase toward TP53-CDKN1A (PMID:27702651); and protein levels are set by UCHL1- and USP13-dependent ubiquitin-proteasome turnover (PMID:28392346, PMID:27869170). MITF chromatin access at a subset of enhancers requires TFAP2 paralogs acting as pioneer factors (PMID:35580127), and its own transcription is set by p300, MED23, PGC-1α/β, BMAL1, Zeb1, STAT3/CEBP and autorepression (PMID:23201126, PMID:33323974, PMID:30910803, PMID:28834744, PMID:34160901). Truncating MITF mutations that abolish DNA binding cause Waardenburg syndrome type 2 through haploinsufficiency (PMID:9170159).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1997 High

    Established that MITF is an instructive determinant of melanocyte identity and that its disease mutations act through loss of DNA binding rather than dominant interference.

    Evidence Ectopic MITF expression in NIH/3T3 fibroblasts inducing melanocyte markers, plus DNA-binding and tyrosinase reporter assays on WS2 truncation mutants

    PMID:9170159

    Open questions at the time
    • Did not define the endogenous enhancer/promoter network MITF engages
    • Mechanism of haploinsufficiency dosage sensitivity not resolved
  2. 2001 High

    Showed MITF is a signal-responsive effector, placing it downstream of M-CSF/MAPK in osteoclast development via phosphorylation-dependent coactivator recruitment.

    Evidence MAPK-site mutagenesis, co-IP with p300, and osteoclast reconstitution in Mitf(mi/mi) bone marrow

    PMID:11684011

    Open questions at the time
    • Did not map all co-occupied promoters
    • Relationship to other lineage cofactors not addressed
  3. 2003 High

    Defined direct melanocyte differentiation targets of MITF, anchoring its role in pigment-cell gene expression.

    Evidence EMSA, ChIP, reporter assays and endogenous modulation of SILV and MLANA in melanoma cells

    PMID:12819038

    Open questions at the time
    • Genome-wide target scope not established
    • Did not address combinatorial enhancer logic
  4. 2004 High

    Revealed that MITF couples melanocyte differentiation to cell-cycle exit through direct INK4A/p16 activation and Rb cooperation.

    Evidence ChIP, reporter assays, Rb phosphorylation Western blots and differentiation assays (with related p21/Rb1 study in 2005)

    PMID:15623583 PMID:15716956

    Open questions at the time
    • Did not reconcile pro-differentiation arrest with proliferative roles in other contexts
    • Switch between activation and repression of growth genes unexplained
  5. 2004 High

    Identified SUMOylation and S409 phosphorylation as context-dependent modulators of MITF transcriptional output and cofactor partitioning.

    Evidence SUMO modification and mutagenesis with promoter-context reporter assays; co-IP showing PIAS3 shuttling from MITF to STAT3 in MITF(di/di) mice

    PMID:15507434 PMID:15572665

    Open questions at the time
    • The SUMO ligase and deconjugase machinery for MITF not identified
    • Synergy-control model not tested genome-wide
  6. 2006 High

    Connected MITF dosage to invasive behavior, showing it activates DIAPH1 and c-Met to control actin dynamics and HGF-dependent invasion.

    Evidence Reporter/ChIP assays, knockdown and overexpression, dominant-negative MITF, and matrix/cell invasion assays in melanoma cells

    PMID:16455654 PMID:17182868

    Open questions at the time
    • Quantitative dose thresholds for the invasive switch not defined
    • Did not integrate with repressed pro-invasion targets identified later
  7. 2011 High

    Linked the germline E318K variant to a SUMO-defective gain-of-function MITF with expanded genome occupancy, providing a molecular basis for melanoma predisposition.

    Evidence SUMO assays, ChIP and genome-wide occupancy profiling, and clonogenicity/migration/invasion assays across two independent reports

    PMID:22012259 PMID:22080950

    Open questions at the time
    • Why loss of a single SUMO site globally increases occupancy mechanistically unresolved
    • Cooperating genetic events not defined
  8. 2015 High

    Expanded MITF function beyond transcription into organelle biology, showing it drives endolysosomal biogenesis that amplifies Wnt signaling in a feedback loop.

    Evidence Inducible MITF expression, late-endosomal immunofluorescence, Wnt reporter assays and C-terminal GSK3 phosphosite mapping

    PMID:25605940

    Open questions at the time
    • Whether MVB sequestration generalizes beyond melanoma not tested
    • Stoichiometry of destruction-complex sequestration unknown
  9. 2018 High

    Defined the dual-phosphorylation export switch and the structural/karyophilic determinants of MITF localization and stability.

    Evidence Phosphosite mapping, mutagenesis and nuclear export assays (BRAF priming + GSK3); NLS mapping and stability assays of bHLH-Zip mutants

    PMID:29938923 PMID:30150413

    Open questions at the time
    • Export receptor recognizing the hydrophobic signal not identified
    • mTOR-controlled export of non-melanocyte isoforms not mechanistically dissected
  10. 2019 High

    Resolved the structural basis of CLEAR-box recognition and established MITF as a direct controller of lysosomal/autophagosomal gene programs and starvation autophagy.

    Evidence Crystal structure of MITF on the CLEAR-box, ChIP-seq, and autophagy flux assays with knockdown/overexpression

    PMID:30705290

    Open questions at the time
    • Overexpression alone insufficient for autophagic flux—the limiting cofactor unidentified
    • Relationship to TFE family redundancy not addressed
  11. 2019 Medium

    Implicated MITF in metabolic control through autorepression, SDHB regulation, and HIF1α-dependent co-regulation of hypoxia targets.

    Evidence ChIP-seq, hypoxia gene-expression profiling, metabolite measurement and knockdown/overexpression

    PMID:31207090

    Open questions at the time
    • Single-lab study not independently confirmed
    • Direct mechanism of autorepression not structurally defined
  12. 2021 High

    Established MITF as a driver of immune evasion, directly activating ADAM10 to shed NK ligands, and refined its repressive control over ECM/adhesion programs.

    Evidence ChIP-seq/qPCR with CRISPR editing of the MITF binding site and NK cytotoxicity assays (ADAM10); ChIP-seq and focal-adhesion quantification for repressed targets

    PMID:33438577 PMID:33789714

    Open questions at the time
    • In vivo contribution of ADAM10 axis to immune escape not quantified
    • Co-repressors mediating ECM-gene silencing not identified
  13. 2022 High

    Identified TFAP2A/C as pioneer factors required for MITF chromatin access at a subset of enhancers, explaining context-dependent target selection.

    Evidence TFAP2A/C knockout with MITF/TFAP2 ChIP-seq, ATAC-seq, H3K27Ac/H3K27Me3 profiling and gene-expression analysis

    PMID:35580127

    Open questions at the time
    • Which enhancers require TFAP2 versus other pioneers not fully cataloged
    • Mechanism of cooperative loading at the nucleosome unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many upstream inputs (SUMO state, MAPK/GSK3/AKT phosphorylation, ubiquitin turnover, pioneer-factor availability, and signal-driven transcription) are integrated to set MITF dosage and direct activation versus repression at specific loci genome-wide remains unresolved.
  • No unified model of how PTM combinations encode target specificity
  • Quantitative dose-response defining rheostat thresholds not established
  • Degree of redundancy with TFE family proteins in human cells not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 2 R-HSA-168256 Immune System 1
Partners
CTNNB1EP300PIAS3RB1STAT3TFAP2ATFAP2CTP53

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 MITF directly transcriptionally activates the DIAPH1 gene encoding the formin Dia1, which promotes actin polymerization. Low MITF levels reduce Dia1 expression, reorganize the actin cytoskeleton, and increase ROCK-dependent invasiveness; high MITF expression decreases invasiveness. Additionally, MITF regulation of Dia1 controls p27(Kip1)-dependent G1 arrest, linking MITF to both invasiveness and proliferation control. Transcriptional reporter assays, siRNA knockdown, overexpression in melanoma cells, cell invasion assays Genes & development High 17182868
2005 MITF acts as an anti-proliferative transcription factor by directly activating the p21(Cip1)/CDKN1A cyclin-dependent kinase inhibitor gene, inducing G1 cell-cycle arrest. Cooperation between MITF and the retinoblastoma protein Rb1 potentiates MITF-mediated transcriptional activation, and this cooperation is disrupted by melanoma-associated mutations in INK4a or BRAF. Transcriptional reporter assays, ChIP, loss-of-function/gain-of-function in melanocytes and melanoma cells, cell cycle analysis Nature High 15716956
2004 MITF is subject to SUMO modification at conserved lysine residues within SUMO consensus sites. Mutation of these sites significantly affects transcriptional activity of MITF but does not alter dimerization, DNA binding, stability, or nuclear localization. The functional consequences of sumoylation depend on promoter context (synergy control model): differences in transcriptional activity between wild-type and non-sumoylatable MITF are seen only on promoters with multiple MITF binding sites. SUMO modification assays, mutagenesis of sumoylation sites, luciferase reporter assays, dimerization and DNA-binding assays in vitro The Journal of biological chemistry High 15507434
2011 A germline missense substitution in MITF (E318K) located within a SUMO consensus site severely impairs SUMOylation of MITF. The SUMOylation-defective Mi-E318K mutant shows enhanced MITF protein binding to the HIF1A promoter, increased transcriptional activity, and a global increase in MITF-occupied loci compared to wild-type MITF, consistent with a gain-of-function mechanism. SUMO modification assays, ChIP, gene expression profiling, clonogenicity/migration/invasion assays in cell lines Nature High 22012259 22080950
2004 MITF directly binds the INK4A (CDKN2A) promoter, activates p16(Ink4a) mRNA and protein expression, induces retinoblastoma protein hypophosphorylation, and thereby triggers cell cycle arrest. MITF-driven INK4A activation was required for efficient melanocyte differentiation, linking melanocyte differentiation to cell cycle exit through MITF. ChIP, luciferase reporter assays, MITF overexpression/knockdown, Western blot for Rb phosphorylation, differentiation assays The Journal of cell biology High 15623583
2001 M-CSF/macrophage colony-stimulating factor induces phosphorylation of Mitf and TFE3 via a conserved MAPK consensus site, triggering their recruitment of the coactivator p300. An unphosphorylatable Mitf mutant at the MAPK consensus serine specifically fails to support formation of multinucleated osteoclasts, mimicking the defect in Mitf(mi/mi) mice, placing Mitf downstream of M-CSF signaling in osteoclast development. Phosphorylation assays, co-immunoprecipitation with p300, mutagenesis, osteoclast differentiation assays in Mitf(mi/mi) bone marrow cultures Molecular cell High 11684011
2007 MITF and PU.1 co-occupy promoters of osteoclast target genes (e.g., cathepsin K, acid phosphatase 5) in bone marrow-derived precursors in response to CSF-1. RANKL + CSF-1 signaling recruits MAPK-phosphorylated forms of MITF, p38 MAPK, and SWI/SNF chromatin-remodeling complexes to these promoters and markedly increases gene expression. NFATc1 is subsequently recruited to these complexes during terminal osteoclast differentiation. ChIP, co-immunoprecipitation, genetic analysis in Mitf and Pu.1 mutant mice, gene expression assays The Journal of biological chemistry High 17403683
2003 MITF directly transcriptionally regulates the melanoma diagnostic antigens SILV/PMEL17/GP100 and MLANA/MART1. Both gene promoters contain conserved MITF consensus DNA sequences that are bound by MITF in vitro (EMSA) and in vivo (ChIP), and up- or down-regulation of MITF produces corresponding changes in endogenous SILV and MLANA expression. EMSA, ChIP, luciferase reporter assays, siRNA knockdown and overexpression of MITF in melanoma cells The American journal of pathology High 12819038
2006 c-Met (HGF receptor) is a direct transcriptional target of MITF. MITF binds the human c-Met promoter in vivo (ChIP) and adenovirally expressed MITF modulates endogenous c-Met protein levels in melanocytes. Disruption of MITF blocked HGF-dependent increases in c-Met mRNA/protein, indicating HGF regulates its own receptor levels via MITF. Dominant-negative inhibition of MITF resulted in resistance to HGF-dependent matrix invasion. ChIP, adenoviral overexpression, MITF dominant-negative constructs, matrix invasion assays, Western blot The Journal of biological chemistry High 16455654
2018 BRAF/MAPK signaling phosphorylates the melanocyte MITF-M isoform, which primes for subsequent phosphorylation by GSK3 (downstream of PI3K and Wnt). Dual phosphorylation (but not monophosphorylation) promotes MITF nuclear export by activating a previously unrecognized hydrophobic export signal. Non-melanocyte MITF isoforms show poor regulation by MAPK but their export is controlled by mTOR. Phosphorylation mapping, mutagenesis, nuclear export assays, kinase inhibitor treatments, mass spectrometry Proceedings of the National Academy of Sciences of the United States of America High 30150413
2015 MITF expression drives endolysosomal biogenesis in melanoma cells by upregulating lysosomal genes. This leads to a marked increase in multivesicular body (MVB) formation that sequesters the Wnt destruction complex (Axin1, phospho-LRP6, phospho-β-catenin, GSK3) upon Wnt stimulation, enhancing Wnt signaling. MITF protein is stabilized by Wnt signaling through novel C-terminal GSK3 phosphorylation sites, generating a positive feedback loop. Tetracycline-inducible MITF expression, immunofluorescence for late endosomal proteins, Wnt reporter assays, phosphorylation mapping, colocalization studies Proceedings of the National Academy of Sciences of the United States of America High 25605940
2019 MITF binds the CLEAR-box element in the promoters of lysosomal and autophagosomal genes in melanocytes and melanoma cells. Crystal structure of MITF bound to the CLEAR-box reveals that the palindromic nature of this motif induces symmetric MITF homodimer binding. Depletion of MITF attenuates starvation-induced autophagy, while overexpression increases autophagosome numbers but is insufficient to induce autophagic flux. Crystal structure determination, ChIP-seq, MITF knockdown and overexpression, autophagy flux assays Scientific reports High 30705290
2004 In mast cells stimulated via gp130 receptor, MITF is phosphorylated at S409. This phosphorylation of MITF leads to PIAS3 dissociation from MITF and association of PIAS3 with STAT3, mobilizing PIAS3 from MITF to STAT3. In MITF(di/di) mice lacking the Zip domain (the PIAS3-binding domain of MITF), mRNA levels of genes regulated by either MITF or STAT3 are downregulated. Phosphorylation assays, co-immunoprecipitation, genetic analysis in MITF(di/di) mice, gene expression assays Molecular and cellular biology High 15572665
2018 The bHLH-Zip domain of MITF-M contains three karyophilic signals (residues 197–206, 214–217, 255–265). Neither DNA binding nor dimerization is required for nuclear localization of MITF-M. Dimerization-deficient MITF-M mutants show significantly reduced stability in melanoma cells compared to wild-type protein, indicating the bHLH-Zip domain modulates both subcellular localization and protein stability. Mutational analysis of nuclear localization signals, structural characterization, nuclear localization assays, protein stability assays in melanoma cells Pigment cell & melanoma research Medium 29938923
2011 KIT signaling in mast cells markedly upregulates MITF protein without significantly changing MITF mRNA levels, indicating posttranscriptional regulation. KIT signaling downregulates miR-539 and miR-381, miRNAs that repress MITF expression through conserved binding sites in the MITF 3'-UTR. MITF is required for the proliferative phenotype in mast cells, as shRNA knockdown inhibited colony-forming activity. miRNA array, luciferase 3'-UTR reporter assays, miRNA overexpression, shRNA knockdown, colony-forming assays Blood High 21273305
2016 MITF directly activates BPTF gene transcription by binding to the BPTF promoter (validated by ChIP), and MITF overexpression upregulates BPTF and BPTF-regulated genes including BCL2. Suppression of cell growth mediated by MITF silencing is rescued by overexpression of BPTF cDNA, placing BPTF downstream of MITF in the pro-survival signaling cascade. ChIP, luciferase reporter assays, MITF overexpression and shRNA knockdown, rescue experiment with BPTF cDNA Proceedings of the National Academy of Sciences of the United States of America High 27185926
2012 PGC-1α and PGC-1β coactivators are critical for α-MSH–induced MITF expression in melanocytes. α-MSH signaling strongly induces PGC-1α expression and stabilizes both PGC-1α and PGC-1β proteins, which in turn directly activate the MITF promoter. Inhibition of PGC-1α and PGC-1β blocks α-MSH–mediated induction of MITF and melanogenic genes. PGC-1 overexpression and siRNA knockdown, MITF promoter reporter assays, α-MSH stimulation, gene expression analysis, transgenic animals Molecular cell High 23201126
2016 AKT phosphorylates MITF at Serine 510. Phosphorylated MITF-S510 enhances its affinity for TP53 and promotes CDKN1A (p21) expression. Non-phosphorylated MITF promotes TYR (tyrosinase) expression instead, revealing a bifunctional switch in MITF target gene regulation depending on AKT activity. Kinase assays, co-immunoprecipitation, mutagenesis of S510, luciferase reporter assays, Western blot The international journal of biochemistry & cell biology Medium 27702651
2019 MITF directly represses its own transcription (autorepression) and directly regulates SDHB to control the TCA cycle and suppress pseudo-hypoxia. Under hypoxia, MITF is transiently upregulated by HIF1α and co-regulates a subset of HIF targets including VEGFA. ChIP-seq, gene expression analysis under hypoxia, knockdown/overexpression of MITF, metabolite measurement Pigment cell & melanoma research Medium 31207090
2017 UCHL1 negatively regulates MITF protein stability by binding to ubiquitinated MITF and promoting its proteasomal degradation. UCHL1 knockdown upregulates MITF protein (but not mRNA), and proteasome inhibitor MG132 prevents UCHL1-mediated MITF reduction. UCHL1 overexpression suppresses MITF-dependent melanogenesis genes. siRNA knockdown, adenoviral overexpression, proteasome inhibitor treatment, co-immunoprecipitation of ubiquitinated MITF, Western blot The Journal of investigative dermatology Medium 28392346
2016 Androgen receptor (AR) promotes MITF protein degradation through modulation of the miRNA-539-3p/USP13 signaling axis; AR reduces de-ubiquitination of MITF by decreasing USP13 activity via miRNA-539-3p, leading to decreased MITF levels, which shifts the MITF/AXL balance and promotes melanoma cell invasion. Restoring MITF reverses AR-enhanced invasion. AR and USP13 manipulation, MITF protein stability assays, ubiquitination assays, invasion assays, rescue experiments Oncogene Medium 27869170
2021 MITF directly transcriptionally activates ADAM10 (a sheddase that cleaves MICA/B NK cell ligands), as established by ChIP-seq, ChIP-qPCR, CRISPR-Cas9 editing of the MITF binding site, and luciferase reporter assays. High MITF-expressing melanoma cells escape NK cell killing by shedding MICA/B via ADAM10, whereas MITF-low cells are susceptible to NK-mediated killing. ChIP-seq, ChIP-qPCR, CRISPR-Cas9 genome editing, luciferase reporter assays, flow cytometry, NK cytotoxicity assays Journal of experimental & clinical cancer research High 33789714
2021 MITF directly represses the expression of genes associated with extracellular matrix (ECM) remodeling, focal adhesion pathways, and EMT regulators such as CDH2 in melanoma cells. MITF knockdown increases the number of focal adhesion points, a feature of drug-resistant melanomas. These effects are reversible, consistent with the MITF rheostat model. MITF knockdown, ChIP-seq for direct repression targets, focal adhesion quantification, gene expression profiling, morphology analysis eLife High 33438577
2022 TFAP2 paralogs (TFAP2A and TFAP2C) are required for MITF binding and chromatin accessibility at a subset of enhancers near pigmentation and proliferation genes in melanoma cells. Deletion of TFAP2A and TFAP2C abolishes MITF chromatin binding at co-operative enhancers, reduces H3K27Ac marks, and impairs MITF-driven activation of pigmentation genes, revealing TFAP2 as a pioneer factor for MITF. TFAP2A/C knockout, ChIP-seq for MITF and TFAP2A, ATAC-seq for chromatin accessibility, H3K27Ac and H3K27Me3 ChIP-seq, gene expression analysis PLoS genetics High 35580127
2020 STAT3 suppresses MITF transcription through induction of CEBP family member transcription factors (CEBPa/b), which bind to the MITF enhancer region and silence the MITF locus. ATAC-seq confirmed CEBPa/b binding at the MITF enhancer causes epigenetic silencing. Loss of STAT3 in mouse melanoma leads to upregulation of MITF and reduced metastasis. Conditional Stat3 knockout in mouse melanoma, whole-genome expression profiling, ATAC-seq, 3D melanoma models, CEBP ChIP-seq Oncogene High 33323974
2018 MITF-MIR211 constitutes a feed-forward autophagy amplification loop. Under stress (starvation or mTOR inhibition), MITF translocates to the nucleus and upregulates MIR211. MIR211 directly targets RICTOR (an mTORC2 component), inhibiting the mTORC1 pathway, which further stimulates MITF nuclear translocation, completing a positive feedback loop that sustains autophagic activity. mTOR inhibition and starvation assays, MITF nuclear translocation imaging, MIR211 overexpression, luciferase 3'-UTR reporter assay for RICTOR, autophagy flux assays Autophagy Medium 30290719
2019 p300 histone acetyltransferase directly controls MITF transcription through histone acetylation within proximal MITF gene regulatory regions in melanoma cells. Targeted chemical inhibition of p300 acetyltransferase activity suppresses MITF expression and reduces melanoma cell proliferation. FOXM1 was identified as a key downstream effector of the p300-MITF axis. p300 genetic and chemical inhibition, ChIP for histone acetylation at MITF locus, gene expression analysis, proliferation assays Cancer research Medium 30910803
2009 Zeb1 transcription factor binds the Mitf-A promoter in vivo (ChIP) and represses Mitf expression. Heterozygous Zeb1 mutation or shRNA knockdown prevents Mitf repression during RPE dedifferentiation, thereby maintaining Mitf expression and pigmented epithelial morphology. This identifies a regulatory axis linking cell-cell contact signals to Mitf via Zeb1. ChIP at Mitf-A promoter, Zeb1 heterozygous mouse model, lentiviral shRNA knockdown, RT-PCR, cell morphology analysis Investigative ophthalmology & visual science Medium 19515996
2004 STAT3 and MITF cooperatively bind and upregulate the c-fos promoter in NIH-3T3 cells, leading to anchorage-independent growth (cellular transformation). ChIP confirmed both STAT3 and MITF bind the c-fos promoter, and dominant-negative AP-1 (c-fos/c-jun) suppressed transformation by STAT3C + MITF. Retroviral cDNA library screen, promoter luciferase assays, ChIP, soft-agar colony assays, dominant-negative AP-1 suppression Oncogene Medium 14737107
2017 MITF directly regulates the ABCB5 transporter gene, with β-catenin acting as a key activator and co-factor for MITF at the ABCB5 locus. ABCB5 expression is primarily associated with melanoma cells exhibiting differentiation markers (MITF-high state), contrary to its previous characterization as a dedifferentiated stem cell marker. ChIP, β-catenin co-activation assays, gene expression analysis in melanoma cell lines Pigment cell & melanoma research Medium 31595650
2017 The Mediator subunit MED23 controls MITF expression by modulating a distal MITF enhancer. Loss of Med23 impairs pigmentation in melanocyte lineage cells and in zebrafish, and enhances nucleotide excision repair (NER) by de-repressing NER factor expression, revealing that the MED23/MITF axis couples DNA repair to pigmentation. Med23 knockout, MITF enhancer reporter assays, ChIP for NER factors, zebrafish pigmentation rescue, UV DNA damage assays Cell reports High 28834744
2021 BMAL1 (circadian clock protein) binds the promoter region of MITF and transcriptionally regulates its expression in a rhythmic (24-hr periodicity) manner. BMAL1-driven MITF expression positively influences melanin synthesis and BMAL1 overexpression increases melanin levels that protect melanoma cells from UVB-mediated DNA damage. Circadian synchronization, ChIP at MITF promoter, BMAL1 overexpression, melanin quantification, UVB damage assays Pigment cell & melanoma research Medium 34160901
2005 MITF splice isoforms containing exon 6a (the alternatively spliced hexapeptide upstream of the DNA-binding basic domain) have stronger inhibitory effects on DNA synthesis than isoforms lacking exon 6a. The anti-proliferative activity of (+)MITF depends on the aminoterminus and is modulated by serine-73 phosphorylation, and is not dependent on direct E-box binding. BrdU incorporation assays, FACS cell cycle analysis, transient transfection of MITF isoform mutants, mutagenesis of phosphorylation sites Pigment cell research Medium 16162175
1997 Ectopic MITF expression converts NIH/3T3 fibroblasts into cells with melanocyte characteristics (dendritic morphology, tyrosinase, TRP-1 expression), demonstrating MITF's instructive role in melanocyte differentiation. WS2-associated truncating mutations in MITF lose DNA-binding activity and fail to transactivate the tyrosinase promoter, but do not show dominant-negative effects on wild-type MITF activity, supporting haploinsufficiency as the disease mechanism. Transfection of MITF and mutants into NIH/3T3 fibroblasts, melanocyte marker expression, DNA-binding assays, luciferase reporter assays Pigment cell research High 9170159

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 MITF: master regulator of melanocyte development and melanoma oncogene. Trends in molecular medicine 868 16899407
2006 Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Genes & development 477 17182868
2011 A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature 422 22012259
2011 A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 351 22080950
2019 MITF-the first 25 years. Genes & development 322 31123060
2005 Mitf cooperates with Rb1 and activates p21Cip1 expression to regulate cell cycle progression. Nature 308 15716956
2014 MITF in melanoma: mechanisms behind its expression and activity. Cellular and molecular life sciences : CMLS 253 25433395
2004 Mi-2/NuRD: multiple complexes for many purposes. Biochimica et biophysica acta 244 15020045
2003 MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. The American journal of pathology 233 12819038
2000 MITF: a stream flowing for pigment cells. Pigment cell research 226 10952390
2004 MITF links differentiation with cell cycle arrest in melanocytes by transcriptional activation of INK4A. The Journal of cell biology 198 15623583
2015 MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells. Proceedings of the National Academy of Sciences of the United States of America 196 25605940
2011 Hypoxia and MITF control metastatic behaviour in mouse and human melanoma cells. Oncogene 156 21996743
2001 Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation. The journal of investigative dermatology. Symposium proceedings 152 11764295
2006 c-Met expression is regulated by Mitf in the melanocyte lineage. The Journal of biological chemistry 143 16455654
2007 MITF and PU.1 recruit p38 MAPK and NFATc1 to target genes during osteoclast differentiation. The Journal of biological chemistry 142 17403683
2001 Duplicate mitf genes in zebrafish: complementary expression and conservation of melanogenic potential. Developmental biology 139 11543618
2005 Elevated expression of MITF counteracts B-RAF-stimulated melanocyte and melanoma cell proliferation. The Journal of cell biology 135 16129781
2004 Sumoylation of MITF and its related family members TFE3 and TFEB. The Journal of biological chemistry 134 15507434
2001 Linkage of M-CSF signaling to Mitf, TFE3, and the osteoclast defect in Mitf(mi/mi) mice. Molecular cell 129 11684011
2012 Mutations in MITF and PAX3 cause "splashed white" and other white spotting phenotypes in horses. PLoS genetics 116 22511888
2018 MITF and UV responses in skin: From pigmentation to addiction. Pigment cell & melanoma research 112 30019545
1998 Role of Mitf in differentiation and transdifferentiation of chicken pigmented epithelial cell. Developmental biology 106 9466887
2016 Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway. Autophagy 92 26761346
2012 PGC-1 coactivators regulate MITF and the tanning response. Molecular cell 85 23201126
2011 Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors. Molecular and cellular biochemistry 84 21519923
2005 Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform. Gene 80 15715979
2014 Pro-survival role of MITF in melanoma. The Journal of investigative dermatology 79 25142731
2019 MITF has a central role in regulating starvation-induced autophagy in melanoma. Scientific reports 78 30705290
2022 MITF in Normal Melanocytes, Cutaneous and Uveal Melanoma: A Delicate Balance. International journal of molecular sciences 73 35682684
2015 The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis. Pharmacological research 73 26003288
2015 MITF Modulates Therapeutic Resistance through EGFR Signaling. The Journal of investigative dermatology 72 25789707
1998 A big gene linked to small eyes encodes multiple Mitf isoforms: many promoters make light work. Pigment cell research 71 9870544
2021 MITF reprograms the extracellular matrix and focal adhesion in melanoma. eLife 70 33438577
2018 BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export. Proceedings of the National Academy of Sciences of the United States of America 65 30150413
2001 Cochlear melanocytes and MITF signaling. The journal of investigative dermatology. Symposium proceedings 64 11764294
2011 KIT signaling regulates MITF expression through miRNAs in normal and malignant mast cell proliferation. Blood 63 21273305
2008 Gpnmb is a melanoblast-expressed, MITF-dependent gene. Pigment cell & melanoma research 61 18983539
1997 Evidence to suggest that expression of MITF induces melanocyte differentiation and haploinsufficiency of MITF causes Waardenburg syndrome type 2A. Pigment cell research 58 9170159
2021 NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism. Cell 55 34233163
2019 MITF controls the TCA cycle to modulate the melanoma hypoxia response. Pigment cell & melanoma research 55 31207090
2004 Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes. Molecular and cellular biology 55 15572665
2020 STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway. Oncogene 52 33323974
2009 Zeb1 represses Mitf and regulates pigment synthesis, cell proliferation, and epithelial morphology. Investigative ophthalmology & visual science 52 19515996
1993 Amiodarone and post-MI patients. Circulation 51 7687937
2019 The transcription factor MITF in RPE function and dysfunction. Progress in retinal and eye research 50 31242455
2017 miRNA-340 inhibits osteoclast differentiation via repression of MITF. Bioscience reports 50 28607030
2008 UV radiation regulates Mi-2 through protein translation and stability. The Journal of biological chemistry 50 18922793
2019 MITF Expression Predicts Therapeutic Vulnerability to p300 Inhibition in Human Melanoma. Cancer research 49 30910803
2016 HMGB1 Inhibits Apoptosis Following MI and Induces Autophagy via mTORC1 Inhibition. Journal of cellular physiology 49 27580416
2016 Androgen receptor promotes melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signals. Oncogene 49 27869170
2017 MITF and BRN2 contribute to metastatic growth after dissemination of melanoma. Scientific reports 48 28883623
2017 Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression. International journal of molecular sciences 47 28880216
2013 MITF mutations associated with pigment deficiency syndromes and melanoma have different effects on protein function. Human molecular genetics 47 23787126
2010 The discovery of the microphthalmia locus and its gene, Mitf. Pigment cell & melanoma research 47 20807369
2004 STAT3 and MITF cooperatively induce cellular transformation through upregulation of c-fos expression. Oncogene 44 14737107
2018 MITF-MIR211 axis is a novel autophagy amplifier system during cellular stress. Autophagy 43 30290719
2011 Differentiated melanocyte cell division occurs in vivo and is promoted by mutations in Mitf. Development (Cambridge, England) 42 21771814
2005 MITF and cell proliferation: the role of alternative splice forms. Pigment cell research 42 16162175
2019 Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease. Cancer research 38 31582381
2021 Mitf Involved in Innate Immunity by Activating Tyrosinase-Mediated Melanin Synthesis in Pteria penguin. Frontiers in immunology 37 34093521
2016 SOX10-MITF pathway activity in melanoma cells. Archives of medical science : AMS 36 29181082
2018 MITF-M regulates melanogenesis in mouse melanocytes. Journal of dermatological science 35 29496358
2013 MITF, the Janus transcription factor of melanoma. Future oncology (London, England) 35 23414473
2016 BPTF transduces MITF-driven prosurvival signals in melanoma cells. Proceedings of the National Academy of Sciences of the United States of America 34 27185926
2020 Cancer risks associated with the germline MITF(E318K) variant. Scientific reports 33 33051548
2016 Phosphorylation of MITF by AKT affects its downstream targets and causes TP53-dependent cell senescence. The international journal of biochemistry & cell biology 33 27702651
2007 Role of microphthalmia transcription factor (Mitf) in melanoma differentiation. Biochemical and biophysical research communications 33 17266927
2002 Regulation of mast cell phenotype by MITF. International archives of allergy and immunology 33 11919417
2022 TFAP2 paralogs facilitate chromatin access for MITF at pigmentation and cell proliferation genes. PLoS genetics 32 35580127
2022 A review of neoplasms with MITF/MiT family translocations. Histology and histopathology 30 35107169
2017 Pathways from senescence to melanoma: focus on MITF sumoylation. Oncogene 30 28825724
2014 Mitf regulates osteoclastogenesis by modulating NFATc1 activity. Experimental cell research 30 25152440
2017 UCHL1 Regulates Melanogenesis through Controlling MITF Stability in Human Melanocytes. The Journal of investigative dermatology 29 28392346
2017 MITF suppression improves the sensitivity of melanoma cells to a BRAF inhibitor. Cancer letters 29 28923400
2013 MITF and PAX3 Play Distinct Roles in Melanoma Cell Migration; Outline of a "Genetic Switch" Theory Involving MITF and PAX3 in Proliferative and Invasive Phenotypes of Melanoma. Frontiers in oncology 29 24062982
2018 Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma. Translational oncology 27 30502589
2015 miR-211 and MITF modulation by Bcl-2 protein in melanoma cells. Molecular carcinogenesis 27 26599548
2013 A germline oncogenic MITF mutation and tumor susceptibility. European journal of cell biology 27 24290354
2002 The function of MITF and associated proteins in mast cells. Molecular immunology 27 12217380
2021 The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis. Cell & bioscience 25 33441180
2018 Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain. Pigment cell & melanoma research 25 29938923
2021 MITF induces escape from innate immunity in melanoma. Journal of experimental & clinical cancer research : CR 23 33789714
2009 Simultaneous suppression of MITF and BRAF V600E enhanced inhibition of melanoma cell proliferation. Cancer science 23 19659611
2021 Involvement of adenylate cyclase/cAMP/CREB and SOX9/MITF in melanogenesis to prevent vitiligo. Molecular and cellular biochemistry 22 33389492
2020 MITF and TFEB cross-regulation in melanoma cells. PloS one 22 32881934
2021 Circadian clock protein BMAL1 regulates melanogenesis through MITF in melanoma cells. Pigment cell & melanoma research 21 34160901
2017 Pyridoxamine improves survival and limits cardiac dysfunction after MI. Scientific reports 21 29167580
2007 Expression and transcriptional activity of alternative splice variants of Mitf exon 6. Molecular and cellular biochemistry 21 17457519
2023 Clear cell tumor with melanocytic differentiation and MITF::CREM translocation. Journal of cutaneous pathology 20 37057373
2019 Delineating the role of MITF isoforms in pigmentation and tissue homeostasis. Pigment cell & melanoma research 20 31562697
2017 Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling. Journal of cellular and molecular medicine 20 28158928
2022 Mi-RNA-93 and Mi-RNA-152 in the Diagnosis of Type 2 Diabetes and Diabetic Retinopathy. British journal of biomedical science 19 35996507
2020 MITF variants cause nonsyndromic sensorineural hearing loss with autosomal recessive inheritance. Scientific reports 19 32728090
2018 A homozygous MITF mutation leads to familial Waardenburg syndrome type 4. American journal of medical genetics. Part A 19 30549420
2014 Enhancement of RANKL-induced MITF-E expression and osteoclastogenesis by TGF-β. Cell biochemistry and function 19 24519885
2019 ABCB5 is activated by MITF and β-catenin and is associated with melanoma differentiation. Pigment cell & melanoma research 18 31595650
2017 Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF. Cell reports 18 28834744
2004 Isolation and developmental expression of Mitf in Xenopus laevis. Developmental dynamics : an official publication of the American Association of Anatomists 18 15108314
2021 Endolysosomal Cation Channels and MITF in Melanocytes and Melanoma. Biomolecules 17 34356645

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