Affinage

MITF

Microphthalmia-associated transcription factor · UniProt O75030

Length
526 aa
Mass
58.8 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MITF is a basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factor that functions as a master regulator of melanocyte differentiation, osteoclast development, endolysosomal biogenesis, and cell cycle control by directly activating lineage-specific genes (tyrosinase, SILV/PMEL17, MLANA, MC1R, GPNMB, ABCB5) as well as genes governing proliferation (INK4A/p16, c-Met, DIAPH1), survival (BPTF, BCL2), and DNA repair (GTF2H1/TFIIH) (PMID:12819038, PMID:15623583, PMID:17182868, PMID:30651597). MITF also directly represses extracellular matrix, focal adhesion, and EMT-associated genes, and its expression level dictates a rheostat-like switch between proliferative and invasive melanoma cell states (PMID:33438577, PMID:17182868). Its activity is controlled post-translationally by SUMOylation that modulates synergistic transcriptional output on multi-site promoters, BRAF/MAPK-primed GSK3 phosphorylation that exposes a nuclear export signal, AKT phosphorylation at S510 that redirects MITF toward TP53/p21 targets, and ubiquitin–proteasome turnover regulated by USP13 and UCHL1 (PMID:15507434, PMID:30150413, PMID:27702651, PMID:27869170, PMID:28392346). Upstream transcriptional control of MITF integrates inputs from PGC-1α/β coactivators (α-MSH signaling), SOX10, TFAP2 paralogs, BMAL1 (circadian regulation), MED23/Mediator, and a STAT3–CEBP epigenetic silencing axis that governs melanoma phenotype switching (PMID:23201126, PMID:35580127, PMID:34160901, PMID:28834744, PMID:33323974).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Establishing that MITF and TFE3 are functionally redundant in osteoclast development resolved why single knockouts had mild bone phenotypes and demonstrated that MiT/TFE family members share essential roles in myeloid lineage differentiation.

    Evidence Double-knockout mouse genetics with bone phenotyping showing severe osteopetrosis only in Mitf/Tfe3 compound nulls

    PMID:11930005

    Open questions at the time
    • Identity of shared versus isoform-specific osteoclast target genes was not resolved
    • Whether TFEB or TFEC also compensate was not tested
  2. 2003 High

    Identification of SILV/PMEL17 and MLANA/MART1 as direct MITF targets via E-box binding established MITF as a direct transcriptional activator of melanocyte differentiation antigens, not merely a lineage marker.

    Evidence EMSA, ChIP, and reporter assays in melanoma cells with endogenous protein validation

    PMID:12819038

    Open questions at the time
    • Genome-wide target repertoire was not yet defined
    • Cofactor requirements for melanocyte-specific activation not addressed
  3. 2004 High

    Three concurrent discoveries expanded MITF's functional scope beyond pigmentation: SUMOylation was shown to tune synergistic transcription on multi-site promoters, INK4A/p16 was identified as a direct target linking MITF to cell cycle arrest and differentiation, and MITF–STAT3 cooperation at c-fos was linked to cellular transformation.

    Evidence In vitro SUMOylation with promoter context mutagenesis; ChIP of INK4A promoter with cell cycle analysis; ChIP of c-fos promoter with soft-agar transformation assay

    PMID:14737107 PMID:15507434 PMID:15572665 PMID:15623583

    Open questions at the time
    • SUMO E3 ligase identity for MITF was not determined
    • Whether INK4A activation is melanocyte-specific or shared with osteoclasts was unclear
    • STAT3 phosphorylation–PIAS3 switch mechanism was characterized only in mast cells and needed melanocyte confirmation
  4. 2006 High

    Identification of DIAPH1 and c-Met as direct MITF targets, together with the rheostat model (low MITF = invasive/arrested, high MITF = proliferative), provided the first mechanistic framework for how MITF expression level controls the switch between proliferation and invasion in melanoma.

    Evidence ChIP, knockdown/overexpression with actin cytoskeleton, proliferation, and invasion readouts; adenoviral MITF modulation with matrix invasion assays

    PMID:16455654 PMID:17182868

    Open questions at the time
    • Whether additional cytoskeletal targets mediate the invasive phenotype was unknown
    • In vivo validation of the rheostat model was lacking
  5. 2006 Medium

    Discovery of a heart-specific MITF isoform induced by β-adrenergic stimulation that drives BNP expression extended MITF function beyond melanocytes and osteoclasts to cardiac hypertrophy.

    Evidence Two MITF mutant mouse strains with echocardiography plus siRNA knockdown with BNP promoter-reporter in cardiomyocytes

    PMID:16998588

    Open questions at the time
    • Cardiac MITF target gene repertoire beyond BNP was not defined
    • Not independently replicated in a second lab
    • Mechanism of cardiac isoform-specific regulation was not resolved
  6. 2007 High

    Demonstrating that MITF and PU.1 form a complex at osteoclast promoters recruited by CSF-1/RANKL with SWI/SNF remodelers, followed by NFATc1, established the ordered chromatin-level mechanism of MITF action in osteoclast terminal differentiation.

    Evidence ChIP at cathepsin K and acid phosphatase 5 promoters, co-immunoprecipitation of MITF–PU.1, genetic mouse models

    PMID:17403683

    Open questions at the time
    • Whether MITF directly recruits SWI/SNF or PU.1 mediates recruitment was unresolved
    • Structural basis of MITF–PU.1 interaction was unknown
  7. 2008 Medium

    Identification of GPNMB as a direct melanoblast target via a conserved MITF-dependent enhancer and demonstration that MITF controls melanosome distribution through Rab27a extended MITF's role to organelle transport beyond transcription of pigment enzymes.

    Evidence In vivo enhancer-reporter with MITF site mutagenesis; dominant-negative MITF in Xenopus melanophores with Rab27a and dendricity quantification

    PMID:18353143 PMID:18983539

    Open questions at the time
    • Direct ChIP of Rab27a by MITF was not shown
    • Whether melanosome transport control is conserved in mammalian melanocytes was not established
  8. 2010 Medium

    Showing that ATF2 suppresses MITF indirectly through JunB-mediated repression of SOX10 placed MITF within a BRAF(V600E)-dependent oncogenic circuit and identified an epistatic relationship between ATF2 and MITF in melanoma transformation.

    Evidence Expression profiling in Atf2−/− mice, epistasis analysis with shRNA combinations, soft-agar assay

    PMID:21203491

    Open questions at the time
    • Direct mechanism by which JunB represses SOX10 transcription was not resolved
    • Whether this axis operates in non-melanoma contexts was unknown
  9. 2011 High

    The germline E318K mutation that abolishes MITF SUMOylation, enhances global transcriptional activity including HIF1A, and increases clonogenicity provided the first direct link between the SUMOylation-deficiency mechanism characterized in 2004 and human cancer predisposition.

    Evidence SUMOylation assays, ChIP, promoter reporters, clonogenicity/migration/invasion assays; replicated in two independent Nature publications

    PMID:22012259 PMID:22080950

    Open questions at the time
    • Which of the >100 dysregulated genes are the critical oncogenic effectors was not determined
    • Whether SUMO-deficient MITF adopts a distinct structural conformation was unknown
  10. 2012 High

    Identification of PGC-1α/β as coactivators of the MITF promoter downstream of α-MSH established a metabolic signaling input to MITF expression and linked mitochondrial regulators to melanogenesis.

    Evidence MITF promoter-reporter, PGC-1 knockdown/overexpression, α-MSH stimulation, transgenic PGC-1α animal

    PMID:23201126

    Open questions at the time
    • Whether PGC-1 coactivation is direct (binding MITF promoter) or through CREB was not fully resolved
    • Role of PGC-1 in osteoclast MITF expression was not tested
  11. 2015 High

    Demonstrating that MITF drives endolysosomal biogenesis and potentiates Wnt signaling through multivesicular body expansion, while itself being stabilized by Wnt-mediated GSK3 inhibition at C-terminal phosphosites, revealed a positive feedback loop connecting MITF to vesicular trafficking and Wnt pathway activity.

    Evidence Inducible MITF expression with vesicle quantification, late endosomal markers, Wnt reporter assays, phosphorylation site mutagenesis

    PMID:25605940

    Open questions at the time
    • Whether the feedback loop operates in non-melanoma cell types was unclear
    • Precise GSK3 phosphosites on MITF C-terminus required mapping
  12. 2016 Medium

    Three studies elucidated distinct post-translational control mechanisms: AKT phosphorylation at S510 redirects MITF from pigmentation targets to TP53/p21-dependent senescence; USP13 deubiquitinates and stabilizes MITF (antagonized by AR via miR-539-3p); and BPTF was identified as a MITF effector transducing pro-survival signaling.

    Evidence Co-IP of MITF-TP53 with phospho-site mutagenesis; USP13-MITF Co-IP with ubiquitination assay and in vivo invasion; ChIP of BPTF promoter with rescue experiments

    PMID:27185926 PMID:27702651 PMID:27869170

    Open questions at the time
    • Whether S510 phosphorylation and SUMOylation are coordinated was not examined
    • UCHL1 and USP13 may have opposing effects on MITF ubiquitination — their interplay was not resolved
    • BPTF's direct transcriptional targets downstream of MITF were not identified
  13. 2017 High

    MITF was shown to directly activate GTF2H1 (TFIIH subunit), connecting it to nucleotide excision repair capacity, while MED23 was found to control MITF expression through distal enhancer activity — together establishing a bidirectional regulatory link between MITF and the general transcription/repair machinery.

    Evidence ChIP and NER functional assays for GTF2H1; Med23 conditional KO in melanocytes with ATAC-seq and NER assays, zebrafish validation

    PMID:28834744 PMID:30651597

    Open questions at the time
    • Whether MITF-driven NER is melanocyte-specific or shared with osteoclasts was not tested
    • Structural basis of MED23 interaction with the MITF enhancer was not resolved
  14. 2017 Medium

    UCHL1 was identified as a negative regulator of MITF stability that promotes proteasomal degradation by binding ubiquitinated MITF, adding a second ubiquitin-editing enzyme (alongside USP13) to the MITF protein turnover mechanism.

    Evidence siRNA/adenoviral UCHL1 modulation, MG132 treatment, Co-IP of UCHL1 with ubiquitinated MITF

    PMID:28392346

    Open questions at the time
    • The E3 ubiquitin ligase(s) targeting MITF for degradation were not identified in this study
    • Whether UCHL1 edits K48- or K63-linked ubiquitin chains on MITF was not determined
  15. 2018 High

    Mapping of MITF nuclear dynamics revealed three karyophilic signals in the bHLH-Zip domain for constitutive import and a BRAF/MAPK-primed, GSK3-dependent hydrophobic nuclear export signal; this dual regulation explained how signaling pathways dynamically control MITF nuclear–cytoplasmic partitioning.

    Evidence Mutagenesis of NLS and NES sequences, subcellular fractionation, kinase inhibitor treatments, isoform comparisons

    PMID:29938923 PMID:30150413

    Open questions at the time
    • Nuclear export receptor (exportin) identity was not determined
    • Whether phosphorylation-dependent export occurs in osteoclasts was not tested
  16. 2018 Medium

    EOMES was identified as a new component of the PU.1–MITF complex at osteoclast gene loci, with EOMES loss phenocopying osteopetrosis, establishing a ternary transcription factor complex for osteoclast differentiation.

    Evidence Co-IP of PU.1–MITF–EOMES, sequential ChIP, EOMES knockdown with in vivo bone phenotyping

    PMID:30634169

    Open questions at the time
    • Whether EOMES directly contacts MITF or interacts only through PU.1 was not resolved
    • Genome-wide co-occupancy of the ternary complex was not mapped
  17. 2020 High

    A STAT3–CEBP axis was shown to epigenetically silence the MITF enhancer by reducing chromatin accessibility, providing a mechanism for the proliferative-to-invasive phenotype switch in melanoma independent of genetic alterations.

    Evidence Stat3 conditional KO mouse, ATAC-seq of MITF enhancer, CEBP knockdown, 3D invasion models

    PMID:33323974

    Open questions at the time
    • Whether CEBP recruits specific chromatin-modifying enzymes to the MITF enhancer was not determined
    • Reversibility of the epigenetic silencing was not fully characterized
  18. 2021 High

    Genome-wide ChIP-seq established that MITF directly represses ECM, focal adhesion, and EMT genes (not just activates lineage genes), providing the molecular basis for the invasive phenotype arising when MITF is lost, and BMAL1 was shown to impose circadian periodicity on MITF transcription with functional consequences for UVB protection.

    Evidence MITF ChIP-seq and RNA-seq with knockdown/overexpression in melanoma; ChIP of MITF promoter by BMAL1 in synchronized cells with melanin and UVB assays

    PMID:33438577 PMID:34160901

    Open questions at the time
    • Mechanisms of MITF-mediated transcriptional repression (corepressor identity) were not determined
    • Whether circadian MITF regulation affects osteoclast or mast cell functions was not tested
  19. 2022 High

    Demonstrating that TFAP2A/C are required for MITF chromatin access at a subset of co-occupied enhancers established that MITF is not autonomous at all its binding sites and requires pioneer-like TFAP2 activity for enhancer activation near pigmentation and proliferation genes.

    Evidence TFAP2A/C double KO in melanoma cells with ChIP-seq, ATAC-seq, histone mark ChIP-seq, and RNA-seq

    PMID:35580127

    Open questions at the time
    • Whether TFAP2 acts as a true pioneer factor or merely co-stabilizes MITF binding was not resolved
    • Whether other lineages (osteoclasts, mast cells) use analogous cofactors for MITF access was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the E3 ubiquitin ligase(s) that target MITF for proteasomal degradation, the structural basis for MITF's context-dependent activation versus repression, and the mechanisms coordinating multiple post-translational modifications (SUMOylation, phosphorylation, ubiquitination) on the same MITF molecule remain unresolved.
  • No E3 ligase for MITF has been identified
  • No high-resolution structure of full-length MITF in complex with DNA and cofactors exists
  • How SUMOylation, multi-site phosphorylation, and ubiquitination are temporally coordinated is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 2
Partners
EOMESPIAS3PU.1STAT3TFAP2ATFAP2CUCHL1USP13
Complex memberships
MITF-PU.1-EOMES osteoclast transcription complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 MITF directly regulates DIAPH1 (Dia1), a diaphanous-related formin that promotes actin polymerization; low MITF levels reduce Dia1, reorganize the actin cytoskeleton, increase ROCK-dependent invasiveness, and cause p27(Kip1)-dependent G1 arrest, whereas high MITF decreases invasiveness and promotes proliferation. Transcriptional reporter assays, ChIP, knockdown/overexpression of MITF in melanoma cells with actin cytoskeleton readouts and proliferation/invasion assays Genes & development High 17182868
2011 A germline MITF E318K missense mutation in the SUMO consensus site severely impairs MITF SUMOylation, enhances MITF binding to the HIF1A promoter, increases transcriptional activity globally, and augments melanocytic and renal cell clonogenicity, migration, and invasion. SUMOylation assays, ChIP, promoter reporter assays, clonogenicity/migration/invasion assays in cell lines, gene expression profiling Nature High 22012259 22080950
2004 SUMO modification of conserved lysine residues in MITF (and paralogs TFE3 and TFEB) alters MITF transcriptional activity in a promoter-context-dependent (synergy control) manner without affecting dimerization, DNA binding, stability, or nuclear localization; effects are seen only on promoters with multiple MITF binding sites. In vitro SUMOylation assays, site-directed mutagenesis of SUMO consensus sites, transcriptional reporter assays with promoters containing variable numbers of MITF sites The Journal of biological chemistry High 15507434
2004 MITF directly binds the INK4A (CDKN2A/p16) promoter, activates p16(Ink4a) mRNA and protein expression, induces Rb hypophosphorylation, and triggers cell cycle arrest; INK4A activation is required for efficient melanocyte differentiation. ChIP of INK4A promoter, reporter assays, MITF overexpression/knockdown with Western blot and cell cycle analysis The Journal of cell biology High 15623583
2006 c-Met is a direct transcriptional target of MITF; MITF binds the c-Met promoter in vivo (ChIP), adenoviral MITF modulates endogenous c-Met protein in melanocytes, and disruption of MITF blocks HGF-dependent upregulation of c-Met and HGF-dependent matrix invasion. ChIP of human c-Met promoter, adenoviral MITF overexpression, dominant-negative MITF inhibition, matrix invasion assays The Journal of biological chemistry High 16455654
2003 MITF directly transcriptionally regulates SILV/PMEL17/GP100 and MLANA/MART1; MITF binds conserved E-box sequences in their promoters in vitro and in vivo, regulates their promoter/enhancer regions in reporter assays, and modulation of MITF levels correspondingly changes endogenous SILV and MLANA expression. EMSA, ChIP, reporter assays, MITF overexpression/knockdown in melanoma cells The American journal of pathology High 12819038
2007 MITF and PU.1 form a complex at osteoclast target gene promoters (cathepsin K, acid phosphatase 5) in response to CSF-1; RANKL/CSF-1 together recruit MAPK-phosphorylated MITF, p38 MAPK, and SWI/SNF chromatin-remodeling complexes to these promoters, followed by NFATc1 during terminal differentiation. ChIP at osteoclast target promoters in bone marrow-derived precursors, co-immunoprecipitation of MITF-PU.1 complexes, genetic mouse model analysis The Journal of biological chemistry High 17403683
2004 STAT3 phosphorylation of MITF at S409 causes PIAS3 to dissociate from MITF and associate with STAT3, thereby modulating transcription of genes regulated by both MITF and STAT3 in mast cells and melanocytes. Immunoprecipitation, phosphorylation assays, transcriptional analysis in MITF(di/di) mice lacking the Zip/PIAS3-binding domain, gp130/c-Kit receptor stimulation Molecular and cellular biology High 15572665
2015 MITF expression drives endolysosomal biogenesis (upregulating Rab7, LAMP1, CD63 and lysosomal gene sets) and potentiates Wnt signaling by increasing multivesicular bodies that sequester the Wnt destruction complex; MITF protein is itself stabilized by Wnt signaling through novel C-terminal GSK3 phosphorylation sites, creating a positive feedback loop. Tetracycline-inducible MITF expression, vesicle quantification, immunofluorescence for late endosomal markers, Wnt reporter assays, phosphorylation site mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 25605940
2018 BRAF/MAPK signaling phosphorylates MITF-M, which primes it for GSK3 phosphorylation (inhibited by PI3K and Wnt); dual phosphorylation activates a hydrophobic nuclear export signal, driving MITF nuclear export. Non-melanocyte MITF isoforms are instead exported in an mTOR-dependent manner. Phosphorylation site mutagenesis, nuclear fractionation, export signal mapping, kinase inhibitor treatments, isoform comparisons Proceedings of the National Academy of Sciences of the United States of America High 30150413
2018 The bHLH-Zip domain of MITF-M contains three karyophilic signals (residues 197–206, 214–217, 255–265) required for constitutive nuclear localization; neither DNA binding nor dimerization is required for nuclear import, but dimerization-deficient mutants show markedly reduced MITF-M protein stability. Mutational analysis of nuclear localization signals, subcellular fractionation, structural characterization, stability assays of dimerization-deficient mutants in melanoma cells Pigment cell & melanoma research High 29938923
2002 MITF regulates MC1R gene expression by binding to a CATGTG E-box in the MC1R promoter; co-expression of MITF cDNA induced ~5-fold MC1R promoter activity in NIH/3T3 cells, and EMSA confirmed MITF-containing protein from melanoma nuclear extracts binds this site. Luciferase reporter assay, EMSA with melanoma nuclear extracts Life sciences Medium 12204775
2008 MITF regulates melanosome distribution and melanophore dendricity in Xenopus melanophores; dominant-negative MITF reduces dendrites, causes melanosome aggregation, and decreases Rab27a expression, placing MITF upstream of Rab27a in melanosome transport control. Dominant-negative and overexpression of MITF in Xenopus neural tube cultures, immunofluorescence for Rab27a, dendricity quantification Pigment cell & melanoma research Medium 18353143
2006 A heart-specific MITF isoform is expressed in cardiomyocytes and induced by beta-adrenergic stimulation (but not by PAX3); MITF mutant mice show reduced cardiac hypertrophy and failure of beta-adrenergic stimulation to induce BNP, and siRNA knockdown of MITF in cardiomyocytes reduces BNP promoter activity. MITF mutant mouse models (two strains), echocardiography, siRNA knockdown with BNP promoter-reporter assay The Journal of clinical investigation Medium 16998588
2002 MITF and TFE3 have functionally redundant roles in osteoclast development; while single Mitf or Tfe3 null mice have normal osteoclasts, combined loss causes severe osteopetrosis, demonstrating genetic epistasis and in vivo functional overlap. Double knockout mouse genetics, bone phenotyping, osteopetrosis quantification Proceedings of the National Academy of Sciences of the United States of America High 11930005
2012 PGC-1α and PGC-1β coactivators directly activate the MITF promoter downstream of α-MSH signaling in melanocytes; α-MSH strongly induces PGC-1α expression and stabilizes PGC-1α/β proteins, and inhibition of PGC-1s blocks α-MSH-mediated induction of MITF and melanogenic genes. MITF promoter-reporter assays, PGC-1 knockdown/overexpression, α-MSH stimulation, transgenic animal overexpression of PGC-1α Molecular cell High 23201126
2016 AKT phosphorylates MITF at S510; phospho-S510 MITF enhances its affinity for TP53 and promotes CDKN1A (p21) expression, whereas unphosphorylated MITF promotes TYR expression; EGF-induced senescence is dependent on this MITF-TP53 interaction. Co-immunoprecipitation of MITF-TP53, phospho-site mutagenesis (S510), luciferase reporter assays, AKT inhibitor treatments The international journal of biochemistry & cell biology Medium 27702651
2016 MITF directly binds the BPTF promoter (demonstrated by ChIP) and transcriptionally activates BPTF; MITF-driven prosurvival signaling (including BCL2) is transduced through BPTF, as BPTF overexpression rescues growth suppression caused by MITF silencing. ChIP of BPTF promoter, luciferase reporter assay, shRNA knockdown, rescue experiments with BPTF cDNA overexpression Proceedings of the National Academy of Sciences of the United States of America Medium 27185926
2021 MITF directly represses genes associated with the extracellular matrix, focal adhesion pathways, and EMT regulators (including CDH2) in melanoma cells; MITF knockdown increases focal adhesion points and produces a drug-resistant morphology similar to minimal residual disease cells. MITF knockdown and overexpression in human melanoma cells with genome-wide ChIP and RNA-seq, focal adhesion immunofluorescence, zebrafish melanoma comparison eLife High 33438577
2010 ATF2 suppresses MITF expression indirectly through an ATF2-JunB-dependent suppression of SOX10 transcription; loss of transcriptionally active ATF2 raises MITF levels and oncogenic BRAF(V600E)-dependent focus formation is rescued by MITF co-depletion. Gene expression profiling in Atf2-/- mice and primary human melanocytes, ATF2/MITF/SOX10 epistasis analysis, soft-agar focus formation assay with shRNA knockdown combinations PLoS genetics Medium 21203491
2004 MITF and STAT3 cooperatively bind and upregulate the c-fos promoter, inducing anchorage-independent growth of NIH-3T3 cells; c-fos induction is required for MITF+STAT3C-driven cellular transformation. Retroviral cDNA library screen, soft-agar colony assay, microarray, ChIP of c-fos promoter, dominant-negative AP-1 rescue Oncogene Medium 14737107
2017 MITF directly transactivates GTF2H1, a core TFIIH subunit required for nucleotide excision repair (NER) and general transcription; MITF also transactivates FUBP2/KSHRP to control c-MYC pulse regulation and maintain CDK7 stability within the TFIIH-CAK subcomplex. ChIP, promoter reporter assays, MITF knockdown with NER and transcription recovery assays, CDK7 protein stability measurements Oncogene High 30651597
2017 Mediator subunit MED23 controls MITF expression by modulating its distal enhancer activity; loss of Med23 impairs pigmentation in melanocyte-lineage cells and zebrafish while paradoxically enhancing NER, establishing a MED23/MITF axis linking DNA repair to pigmentation. Med23 conditional knockout in melanocytes, zebrafish med23 morpholino, ATAC-seq/ChIP of MITF enhancer, NER assays Cell reports Medium 28834744
2017 UCHL1 (ubiquitin carboxyl-terminal hydrolase L1) negatively regulates MITF protein stability by binding to ubiquitinated MITF and promoting its proteasomal degradation, thereby reducing tyrosinase and melanin production in human melanocytes. siRNA knockdown and adenoviral overexpression of UCHL1, proteasome inhibitor (MG132) treatment, protein synthesis inhibition, co-immunoprecipitation of UCHL1-ubiquitinated MITF The Journal of investigative dermatology Medium 28392346
2016 AR (androgen receptor) promotes MITF protein degradation through the miRNA-539-3p/USP13 axis, reducing MITF-driven differentiation and increasing AXL-driven invasion in melanoma; restoring MITF reverses AR-enhanced invasion. miRNA overexpression, USP13 knockdown, Co-IP of USP13-MITF, ubiquitination assay, invasion assays in vitro and mouse model in vivo Oncogene Medium 27869170
2020 STAT3-induced CEBP expression suppresses MITF transcription by epigenetic silencing (CEBP binding to the MITF enhancer region reduces chromatin accessibility, confirmed by ATAC-seq), creating a STAT3-CEBP-MITF axis that drives the proliferative-to-invasive melanoma phenotype switch. Stat3 conditional knockout mouse model, ATAC-seq, genome-wide expression profiling, CEBP knockdown, 3D melanoma models Oncogene High 33323974
2021 BMAL1 directly binds the MITF promoter and transcriptionally regulates MITF expression with 24-hour periodicity in synchronized melanoma cells; BMAL1-driven MITF expression positively influences melanin synthesis and protects from UVB-mediated DNA damage. ChIP of MITF promoter by BMAL1, synchronized circadian clock conditions, BMAL1 overexpression, melanin quantification, UVB survival assays Pigment cell & melanoma research Medium 34160901
2019 MITF directly activates ABCB5 transcription; ABCB5 expression is co-regulated by β-catenin (a known MITF co-activator) and is associated with differentiated melanoma cells rather than de-differentiated stem-like cells. ChIP of ABCB5 promoter by MITF, MITF overexpression/knockdown with ABCB5 mRNA measurements, β-catenin modulation Pigment cell & melanoma research Medium 31595650
2008 Gpnmb is a direct MITF target gene in melanoblasts; a conserved enhancer element (GPNMB-MCS3) containing two MITF consensus sites is sufficient to drive melanoblast expression in vivo, and deletion of the 5'-most MITF site dramatically reduces enhancer activity. Whole-genome MITF binding site annotation, luciferase reporter assays, in vivo enhancer-driven reporter in melanoblasts, deletion mutagenesis of MITF sites Pigment cell & melanoma research Medium 18983539
2022 TFAP2 paralogs (TFAP2A/C) are required for MITF binding and chromatin accessibility at a subset of co-occupied enhancers near pigmentation and proliferation genes in melanoma cells; in TFAP2-KO cells, MITF fails to access these loci and co-operative target gene activation is lost. TFAP2A/C double knockout in SK-MEL-28 cells, ChIP-seq for TFAP2A and MITF, ATAC-seq, H3K27Ac/H3K27Me3 ChIP-seq, RNA-seq PLoS genetics High 35580127
2018 EOMES forms a complex with PU.1 and MITF at osteoclast differentiation gene loci, demonstrated by co-immunoprecipitation and sequential ChIP; EOMES knockdown in myeloid precursors causes osteopetrosis with decreased osteoclast differentiation and function in vitro and in vivo. Co-IP of PU.1-MITF-EOMES complex, sequential ChIP, EOMES knockdown in bone marrow-derived macrophages, in vivo bone phenotyping iScience Medium 30634169

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 862 16899407
2006 Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Genes & development 473 17182868
2011 A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature 420 22012259
2011 A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 349 22080950
2019 MITF-the first 25 years. Genes & development 317 31123060
2014 MITF in melanoma: mechanisms behind its expression and activity. Cellular and molecular life sciences : CMLS 251 25433395
2003 MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. The American journal of pathology 233 12819038
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 194 25605940
2002 Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development. Proceedings of the National Academy of Sciences of the United States of America 193 11930005
2011 Hypoxia and MITF control metastatic behaviour in mouse and human melanoma cells. Oncogene 155 21996743
2001 Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation. The journal of investigative dermatology. Symposium proceedings 151 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 138 11543618
2004 Sumoylation of MITF and its related family members TFE3 and TFEB. The Journal of biological chemistry 132 15507434
2012 Mutations in MITF and PAX3 cause "splashed white" and other white spotting phenotypes in horses. PLoS genetics 115 22511888
2009 Frequent mutations in the MITF pathway in melanoma. Pigment cell & melanoma research 112 19422606
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 83 21519923
2013 A conditional zebrafish MITF mutation reveals MITF levels are critical for melanoma promotion vs. regression in vivo. The Journal of investigative dermatology 81 23831555
2005 Genomic analysis of the Microphthalmia locus and identification of the MITF-J/Mitf-J isoform. Gene 80 15715979
2017 Monolayer WS2 Nanopores for DNA Translocation with Light-Adjustable Sizes. ACS nano 79 28125779
2014 Pro-survival role of MITF in melanoma. The Journal of investigative dermatology 79 25142731
2015 The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis. Pharmacological research 73 26003288
2006 Transcription factor MITF regulates cardiac growth and hypertrophy. The Journal of clinical investigation 72 16998588
2009 Expression of the dermatomyositis autoantigen Mi-2 in regenerating muscle. Arthritis and rheumatism 71 19950298
1998 A big gene linked to small eyes encodes multiple Mitf isoforms: many promoters make light work. Pigment cell research 71 9870544
2022 MITF in Normal Melanocytes, Cutaneous and Uveal Melanoma: A Delicate Balance. International journal of molecular sciences 70 35682684
2013 Phenotypic characterization of nevus and tumor patterns in MITF E318K mutation carrier melanoma patients. The Journal of investigative dermatology 68 23774529
2021 MITF reprograms the extracellular matrix and focal adhesion in melanoma. eLife 67 33438577
2003 Pmel17 expression is Mitf-dependent and reveals cranial melanoblast migration during murine development. Gene expression patterns : GEP 67 14643677
2017 TFAP2 paralogs regulate melanocyte differentiation in parallel with MITF. PLoS genetics 66 28249010
2004 (-)-Epigallocatechin-3-gallate and hinokitiol reduce melanin synthesis via decreased MITF production. Archives of pharmacal research 64 15089040
2002 Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R). Life sciences 64 12204775
2001 Cochlear melanocytes and MITF signaling. The journal of investigative dermatology. Symposium proceedings 64 11764294
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 62 30150413
2002 Immunoprofile of MITF, tyrosinase, melan-A, and MAGE-1 in HMB45-negative melanomas. The American journal of surgical pathology 61 11756773
2008 Gpnmb is a melanoblast-expressed, MITF-dependent gene. Pigment cell & melanoma research 60 18983539
2020 TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS. eLife 59 33300868
2010 A role for ATF2 in regulating MITF and melanoma development. PLoS genetics 59 21203491
2004 Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes. Molecular and cellular biology 55 15572665
2021 NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism. Cell 54 34233163
2017 Glucose availability controls ATF4-mediated MITF suppression to drive melanoma cell growth. Oncotarget 53 28380427
2012 [Regulation of melanogenesis: the role of cAMP and MITF]. Postepy higieny i medycyny doswiadczalnej (Online) 53 22371403
2008 Inhibition of MITF and tyrosinase by paeonol-stimulated JNK/SAPK to reduction of phosphorylated CREB. The American journal of Chinese medicine 51 18457359
1993 Amiodarone and post-MI patients. Circulation 51 7687937
2017 miRNA-340 inhibits osteoclast differentiation via repression of MITF. Bioscience reports 50 28607030
2010 MITF-siRNA formulation is a safe and effective therapy for human melasma. Molecular therapy : the journal of the American Society of Gene Therapy 50 21119619
2020 STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pathway. Oncogene 49 33323974
2019 The transcription factor MITF in RPE function and dysfunction. Progress in retinal and eye research 49 31242455
2016 Androgen receptor promotes melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signals. Oncogene 49 27869170
2008 UV radiation regulates Mi-2 through protein translation and stability. The Journal of biological chemistry 49 18922793
2016 HMGB1 Inhibits Apoptosis Following MI and Induces Autophagy via mTORC1 Inhibition. Journal of cellular physiology 48 27580416
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
2017 Inhibition of NAT10 Suppresses Melanogenesis and Melanoma Growth by Attenuating Microphthalmia-Associated Transcription Factor (MITF) Expression. International journal of molecular sciences 46 28880216
2004 STAT3 and MITF cooperatively induce cellular transformation through upregulation of c-fos expression. Oncogene 43 14737107
2019 Zebrafish MITF-Low Melanoma Subtype Models Reveal Transcriptional Subclusters and MITF-Independent Residual Disease. Cancer research 37 31582381
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
2016 SOX10-MITF pathway activity in melanoma cells. Archives of medical science : AMS 34 29181082
2020 Cancer risks associated with the germline MITF(E318K) variant. Scientific reports 33 33051548
2019 Photoreceptor degeneration in microphthalmia (Mitf) mice: partial rescue by pigment epithelium-derived factor. Disease models & mechanisms 33 30651300
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
2002 Regulation of mast cell phenotype by MITF. International archives of allergy and immunology 33 11919417
2018 A PAX3/BRN2 rheostat controls the dynamics of BRAF mediated MITF regulation in MITFhigh /AXLlow melanoma. Pigment cell & melanoma research 32 30277012
2007 Role of microphthalmia transcription factor (Mitf) in melanoma differentiation. Biochemical and biophysical research communications 32 17266927
2022 A review of neoplasms with MITF/MiT family translocations. Histology and histopathology 30 35107169
2022 TFAP2 paralogs facilitate chromatin access for MITF at pigmentation and cell proliferation genes. PLoS genetics 30 35580127
2017 UCHL1 Regulates Melanogenesis through Controlling MITF Stability in Human Melanocytes. The Journal of investigative dermatology 29 28392346
2017 Pathways from senescence to melanoma: focus on MITF sumoylation. Oncogene 29 28825724
2016 SOX5 is involved in balanced MITF regulation in human melanoma cells. BMC medical genomics 29 26927636
2014 Palmitoylethanolamide inhibits rMCP-5 expression by regulating MITF activation in rat chronic granulomatous inflammation. European journal of pharmacology 29 24440533
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
2018 Subcellular localization and stability of MITF are modulated by the bHLH-Zip domain. Pigment cell & melanoma research 25 29938923
2008 Mitf contributes to melanosome distribution and melanophore dendricity. Pigment cell & melanoma research 25 18353143
2021 The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis. Cell & bioscience 24 33441180
2018 Distribution of mast cells within the mouse heart and its dependency on Mitf. Molecular immunology 24 30471646
2017 Identification of polymorphisms in MITF and DCT genes and their associations with plumage colors in Asian duck breeds. Asian-Australasian journal of animal sciences 24 28823136
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
2018 Eomes partners with PU.1 and MITF to Regulate Transcription Factors Critical for osteoclast differentiation. iScience 22 30634169
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
2021 Circadian clock protein BMAL1 regulates melanogenesis through MITF in melanoma cells. Pigment cell & melanoma research 20 34160901
2017 Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling. Journal of cellular and molecular medicine 20 28158928
2023 Clear cell tumor with melanocytic differentiation and MITF::CREM translocation. Journal of cutaneous pathology 19 37057373
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 Delineating the role of MITF isoforms in pigmentation and tissue homeostasis. Pigment cell & melanoma research 18 31562697
2019 ABCB5 is activated by MITF and β-catenin and is associated with melanoma differentiation. Pigment cell & melanoma research 18 31595650
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
2019 Lineage-specific control of TFIIH by MITF determines transcriptional homeostasis and DNA repair. Oncogene 17 30651597
2017 Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF. Cell reports 17 28834744