Title: Circadian clock protein BMAL1 regulates melanogenesis through MITF in melanoma cells.

Authors: Sarkar, Soumyadeep; Porter, Kenneth I; Dakup, Panshak P; Gajula, Rajendra P; Koritala, Bala S C; Hylton, Ryan; Kemp, Michael G; Wakamatsu, Kazumasa; Gaddameedhi, Shobhan

Published In Pigment Cell Melanoma Res, (2021 09)

Abstract: Solar ultraviolet B radiation (UVB) is one of the leading causes of various skin conditions, including photoaging, sunburn erythema, and melanoma. As a protective response, the skin has inbuilt defense mechanisms, including DNA repair, cell cycle, apoptosis, and melanin synthesis. Though DNA repair, cell cycle, and apoptosis are clock controlled, the circadian mechanisms associated with melanin synthesis are not well understood. Using human melanocytes and melanoma cells under synchronized clock conditions, we observed that the microphthalmia-associated transcription factor (MITF), a rate-limiting protein in melanin synthesis, is expressed rhythmically with 24-hr periodicity in the presence of circadian clock protein, BMAL1. Furthermore, we demonstrated that BMAL1 binds to the promoter region of MITF and transcriptionally regulates its expression, which positively influences melanin synthesis. Finally, we report that an increase in melanin levels due to BMAL1 overexpression protects human melanoma cells from UVB. In conclusion, our studies provide novel insights into the mechanistic role of the circadian clock in melanin synthesis and protection against UVB-mediated DNA damage and genomic instability.

PubMed ID: 34160901

MeSH Terms: ARNTL Transcription Factors/genetics; ARNTL Transcription Factors/metabolism*; Animals; Gene Expression Regulation, Neoplastic*; Humans; Melanoma/genetics; Melanoma/metabolism*; Melanoma/pathology; Mice; Microphthalmia-Associated Transcription Factor/genetics; Microphthalmia-Associated Transcription Factor/metabolism*; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism*