MC1R and NR4A receptors in cellular stress and DNA repair: implications for UVR protection.
Ultraviolet radiation (UVR) is the most common mutagen that melanocytes are exposed to. UVR causes a diverse range of DNA photolesions contributing to genome instability and promotes melanoma and non-melanoma development. Melanocytes are pigment-producing cells that synthesise the photoprotective melanins when the melanocortin-1 receptor (MC1R) is activated. MC1R is a G-protein-coupled receptor expressed predominantly in melanocytes. Its signalling pathway has been directly linked to melanogenesis, enhanced cytoprotection against UV damage and augmented DNA repair response. Interestingly, previous studies have revealed that MC1R signalling induces the transcription of the NR4A subfamily of orphan nuclear receptors in response to UV. In line with this, studies have also observed that NR4A receptors are recruited to distinct nuclear foci in response to cellular stress, independent of their transcriptional roles. Here, we review the regulated expression of NR4A2 and its potential roles upon cellular stress conditions. Current work in developing synthetic NR4A2 agonists further provides exciting avenues for exploring the potential role of NR4A2 as an antiskin cancer drug target.
School of Biomedical Science, The University of Queensland, Brisbane, Qld, Australia.
Kelvin
K
Yin
Richard A
RA
Sturm
Aaron G
AG
Smith
D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008027:Light; D008544:Melanocytes / Q000166:cytology* / Q000528:radiation effects*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism*; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D044102:Receptor, Melanocortin, Type 1; D043562:Receptors, G-Protein-Coupled; D004247:DNA
DNA repair; MC1R; NR4A2; UVR