ArticleThe Journal of biological chemistry2012
Expression of microphthalmia-associated transcription factor (MITF), which is critical for melanoma progression, is inhibited by both transcription factor GLI2 and transforming growth factor-β.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- MITF Is an Essential and Functionally Multifaceted Transcription Factor in Cutaneous Melanoma.Cancers · 2026Review
- SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.International journal of molecular sciences · 2026Review
- DAPL1 inhibits epithelial-mesenchymal transition of retinal pigment epithelial cells by regulating the TGF-β/MITF pathway.Experimental eye research · 2025Article
- Hedgehog Signalling in Osteogenesis and Bone Metabolism: Molecular Mechanisms, Regulatory Networks and Implications for Skeletal Disease.Journal of cellular and molecular medicine · 2025Review
- Transforming Growth Factor-β/Smad Signaling Inhibits Melanoma Cancer Stem Cell Self-Renewal, Tumor Formation and Metastasis.Cancers · 2024Article
- Localized immune surveillance of primary melanoma in the skin deciphered through executable modeling.Science advances · 2023Article
- Reversing Gray Hair: Inspiring the Development of New Therapies Through Research on Hair Pigmentation and Repigmentation Progress.International journal of biological sciences · 2023Review
- Review
- Circadian clock protein BMAL1 regulates melanogenesis through MITF in melanoma cells.Pigment cell & melanoma research · 2021Article
- Hedgehog/GLI Signaling Pathway: Transduction, Regulation, and Implications for Disease.Cancers · 2021Review
- A Missense Mutation in theGenes · 2021Article
- The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis.Cell & bioscience · 2021Review
- Melanoma Plasticity: Promoter of Metastasis and Resistance to Therapy.Frontiers in oncology · 2021Review
- Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives.Cancers · 2020Review
- Isofraxidin: Synthesis, Biosynthesis, Isolation, Pharmacokinetic and Pharmacological Properties.Molecules (Basel, Switzerland) · 2020Review
- MITF-the first 25 years.Genes & development · 2019Review
- Impaired neurodevelopmental pathways in autism spectrum disorder: a review of signaling mechanisms and crosstalk.Journal of neurodevelopmental disorders · 2019Review
- Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer.Frontiers in genetics · 2019Review
- TGF-β2 Induces Gli1 in a Smad3-Dependent Manner Against Cerebral Ischemia/Reperfusion Injury After Isoflurane Post-conditioning in Rats.Frontiers in neuroscience · 2019Article
- A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma.Oncology letters · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The melanocyte-specific transcription factor M-MITF is involved in numerous aspects of melanoblast lineage biology including pigmentation, survival, and migration. It plays complex roles at all stages of melanoma progression and metastasis. We established previously that GLI2, a Kruppel-like transcription factor that acts downstream of Hedgehog signaling, is a direct transcriptional target of the TGF-β/SMAD pathway and contributes to melanoma progression, exerting antagonistic activities against M-MITF to control melanoma cell invasiveness. Herein, we dissected the molecular mechanisms underlying both TGF-β and GLI2-driven M-MITF gene repression. Using transient cell transfection experiments with M-MITF promoter constructs, chromatin immunoprecipitation, site-directed mutagenesis, and electrophoretic mobility shift assays, we identified a GLI2 binding site within the -334/-296 region of the M-MITF promoter, critical for GLI2-driven transcriptional repression. This region is, however, not needed for inhibition of M-MITF promoter activity by TGF-β. We determined that TGF-β rapidly repressed protein kinase A activity, thus reducing both phospho-cAMP-response element-binding protein (CREB) levels and CREB-dependent transcription of the M-MITF promoter. Increased GLI2 binding to its cognate cis-element, associated with reduced CREB-dependent transcription, allowed maximal inhibition of the M-MITF promoter via two distinct mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.