MITF is a novel transcriptional regulator of STIM1: significance in physiological melanogenesis

Stromal Interaction Molecule1 (STIM1) is an endoplasmic reticulum calcium (Ca2+) sensor. Several disease states and enhanced biological phenomena are associated with increased STIM1 levels and activity. However, molecular mechanisms driving STIM1 expression remain largely unappreciated. Here using melanocytes as a model system, we demonstrate that Microphthalmia-associated transcription factor (MITF) is a critical regulator of STIM1 expression and thereby activity. We show that physiological melanogenic stimuli α-Melanocyte Stimulating Hormone (αMSH) increases STIM1 mRNA and protein levels. Further, αMSH stimulates STIM1 promoter-driven luciferase activity, thereby suggesting transcriptional upregulation of STIM1. We report that downstream of αMSH, MITF drives STIM1 expression. By performing knockdown and overexpression studies, we corroborated that MITF regulates STIM1 expression and activity. Next, we conducted extensive bioinformatics analysis and identified MITF binding sites on STIM1 promoter. We validated significance of the MITF binding sites in controlling STIM1 expression by performing ChIP and luciferase assays with truncated STIM1 promoters. Moreover, we confirmed MITF’s role in regulating STIM1 expression in primary human melanocytes. Finally, analysis of publicly available datasets substantiates a positive correlation between STIM1 and MITF expression in sun-exposed tanned human skin, thereby highlighting physiological relevance of this regulation. Taken together, we have identified a novel physiologically relevant molecular pathway that transcriptionally enhances STIM1 expression.


Reference: Tanwar J, Sharma A, Saurav S, Shyamveer, Jatana N and Motiani RK.  MITF is a novel transcriptional regulator of the calcium sensor STIM1: significance in physiological melanogenesis. Journal of Biological Chemistry 2022 Nov 7:102681.


Leave a Reply

Your email address will not be published. Required fields are marked *

Time limit is exhausted. Please reload the CAPTCHA.