Circadian clock protein BMAL1 regulates melanogenesis through MITF in melanoma cells
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 06, 2021
- Source ID
- 10.1111/pcmr.12998
Entities
People
- Bala S C Koritala
- Kazumasa Wakamatsu
- Kenneth I Porter
- Michael G Kemp
- Panshak Dakup
- Rajendra P Gajula
- Ryan Hylton
- Shobhan Gaddameedhi
- Soumyadeep Sarkar
Organizations
- Fujita Health University
- National Institute of Environmental Health Sciences
- United States Department of Defense
- Washington State University
- Wright State University