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Open AccessArticle

Negative Regulatory Loop between Microphthalmia-Associated Transcription Factor (MITF) and Notch Signaling

Department of Human Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
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Int. J. Mol. Sci. 2019, 20(3), 576; https://doi.org/10.3390/ijms20030576
Received: 11 December 2018 / Revised: 24 January 2019 / Accepted: 26 January 2019 / Published: 29 January 2019
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. View Full-Text
Keywords: melanoma; notch signaling; MITF melanoma; notch signaling; MITF
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Golan, T.; Levy, C. Negative Regulatory Loop between Microphthalmia-Associated Transcription Factor (MITF) and Notch Signaling. Int. J. Mol. Sci. 2019, 20, 576.

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