(Boston) – Why are red-haired individuals so proneto developing melanoma? Researchers from Boston University School of Medicine (BUSM) have discovered that MC1R, one of the key genes that regulate a person’s hair and skin color, protects against ultraviolet (UV) damage by direct interaction with PTEN a well-known tumor suppressor protein. These findings appear in the Aug. 22 issue of Molecular Cell.
Clinically, there is a lower incidence of melanoma among individuals with high levels of brown/black pigment and/or acquired pigmentation (i.e. tanning). Conversely, individuals with red hair, blue eyes and an inability to tan are at higher risk for developing melanoma. Mutations of MC1R, such as R151C, R160W and D294H are frequently found to be associated with phenotypes of red hair, fair skin and poor tanning ability (normally called RHC associated phenotype), thus more sensitive to UV exposure.
The researchers found UV exposure triggers MC1R wild type protein but not the RHC associated mutants that interact and protect the tumor suppressor protein PTEN. Specially, MC1R protects UV induced PTEN inactivation by PTEN phosphorylation, PTEN oxidation and WWP2 medicated PTEN degradation.
“Our research establishes that the MC1R-PTEN axis is a central regulator for melanocytes in response to UV exposure and reveals the molecular basis underlying the association between MC1R variants and melanomagenesis,” explained corresponding author Rutao Cui, MD, PhD, associate professor of dermatology at BUSM as well as director of the Pigment Cell Biology Program.
Funding for this study was provided by the National Institutes of Health, the National Cancer Institute, the American Cancer Society and the Harry J. Lloyd Charitable Trust.
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