{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T18:25:58Z","timestamp":1783362358372,"version":"3.54.6"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melanoma, a melanocyte-origin neoplasm, is a highly metastatic and treatment-resistance cancer. While it is well established that notch signaling activation promotes melanoma progression, little is known about the reciprocal interactions between Notch signaling and melanoma-specific pathways. Here we reveal a negative regulatory loop between Notch signaling and microphthalmia-associated transcription factor (MITF), the central regulator of melanoma progression and the driver of melanoma plasticity. We further demonstrate that Notch signaling activation, in addition to the known competition-based repression mechanism of MITF transcriptional activity, inhibits the transcription of MITF, leading to a decrease in MITF expression. We also found that MITF binds to the promoter of the gene encoding the master regulator of Notch signaling, recombination signal binding protein J kappa (RBPJK), leading to its upregulation. Our findings suggest that, once activated, Notch signaling represses MITF signaling to maintain the melanoma invasiveness and metastatic phenotype.<\/jats:p>","DOI":"10.3390\/ijms20030576","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T11:27:52Z","timestamp":1548761272000},"page":"576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Negative Regulatory Loop between Microphthalmia-Associated Transcription Factor (MITF) and Notch Signaling"],"prefix":"10.3390","volume":"20","author":[{"given":"Tamar","family":"Golan","sequence":"first","affiliation":[{"name":"Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmit","family":"Levy","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrc1253","article-title":"Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling","volume":"4","author":"Bowden","year":"2004","journal-title":"Nat. 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