Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells

Smith, Aaron G., Luk, Nicole, Newton, Richard A., Roberts, Donald W., Sturm, Richard A. and Muscat, George E. O. (2008) Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells. The Journal of Biological Chemistry, 283 18: 12564-12570. doi:10.1074/jbc.M800480200

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Author Smith, Aaron G.
Luk, Nicole
Newton, Richard A.
Roberts, Donald W.
Sturm, Richard A.
Muscat, George E. O.
Title Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells
Journal name The Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2008-05-02
Year available 2008
Sub-type Article (original research)
DOI 10.1074/jbc.M800480200
Open Access Status File (Publisher version)
Volume 283
Issue 18
Start page 12564
End page 12570
Total pages 6
Place of publication Baltimore, MD, USA
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject C1
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
060111 Signal Transduction
Abstract The melanocortin-1 receptor (MCIR) is a G-protein-coupled receptor expressed primarily in melanocytes and is known to play a pivotal role in the regulation of pigmentation in mammals. In humans MC1R has been found to be highly polymorphic with several functional variants associated with the phenotype of red hair color and fair skin, cutaneous UV sensitivity, and increased risk of developing melanoma and non-melanoma skin cancer. Recent evidence suggests that MC1R plays a photo-protective role in melanocytes in response to UV irradiation. Relatively few genetic targets of MC1R signaling have been identified independent of the pigmentation pathway. Here we show that MC1R signaling in B16 mouse melanoma cells and primary human melanocytes rapidly, and transiently, induces the transcription of the NR4A subfamily of orphan nuclear receptors. Furthermore, primary human melanocytes harboring homozygous RHC variant MC1R alleles exhibited an impaired induction of NR4A genes in response to the potent MC1R agonist (Nle4,D-Phe7)-α-melanocyte-stimulating hormone. Using small interference RNA-mediated attenuation of NR4A1 and NR4A2 expression in melanocytes, the ability to remove cyclobutane pyrimidine dimers following UV irradiation appeared to be impaired in the context of MC1R signaling. These data identify the NR4A receptor family as potential mediators of an MC1R-coordinated DNA damage response to UV exposure in melanocytic cells.
Keyword MC1R Variant Alleles
Skin-cancer Risk
Skeletal-muscle
Ultraviolet-radiation
Stimulating Hormone
Melanoma-cells
Dna-damage
Red Hair
Human Pigmentation
Ngfi-B
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First Published on February 21, 2008

 
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Created: Tue, 14 Apr 2009, 20:44:21 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience