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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
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 576;
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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MDPI and ACS Style

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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