{"doi":"10.1038/s41598-024-72031-9","title":"MITF regulates IDH1, NNT, and a transcriptional program protecting melanoma from reactive oxygen species","abstract":"Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte function, development and plays a significant role in melanoma pathogenesis. MITF genomic amplification promotes melanoma development, and it can facilitate resistance to multiple therapies. Here, we show that MITF regulates a global antioxidant program that increases survival of melanoma cell lines by protecting the cells from reactive oxygen species (ROS)-induced damage. In addition, this redox program is correlated with MITF expression in human melanoma cell lines and patient-derived melanoma samples. Using a zebrafish melanoma model, we show that MITF decreases ROS-mediated DNA damage in vivo. Some of the MITF target genes involved, such as IDH1 and NNT, are regulated through direct MITF binding to canonical enhancer box (E-BOX) sequences proximal to their promoters. Utilizing functional experiments, we demonstrate the role of MITF and its target genes in reducing cytosolic and mitochondrial ROS. Collectively, our data identify MITF as a significant driver of the cellular antioxidant state.","journal":"Scientific Reports","year":2024,"id":427907,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1178990,"name":"Alexandra I.T. Lakatos","orcid":null,"position":1,"is_corresponding":false},{"id":49578,"name":"Alicia M. 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Graeber","orcid":"0000-0001-8574-9181","position":20,"is_corresponding":false},{"id":49576,"name":"Leonard I. Zon","orcid":"0000-0003-0860-926X","position":21,"is_corresponding":false},{"id":1178530,"name":"Roger W. Giese","orcid":"0000-0003-0515-0692","position":22,"is_corresponding":false},{"id":1229076,"name":"Lajos V Kemeny","orcid":null,"position":23,"is_corresponding":false},{"id":69344,"name":"David E. 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