Modification of a protein involved in the pigmentation process is shown to protect against the development of melanoma in mice, a study published online in Nature this week reports.
The protein melanocortin-1 receptor (MC1R) is known to have an important role in skin pigmentation in humans and mice. However, individuals carrying MC1R RHC variants, including those with red hair colour, fair skin and poor tanning ability, have an associated higher risk of developing melanoma owing to a reduced capacity to induce pigmentation.
By screening several small molecules, Rutao Cui and colleagues show that palmitic acid modulates the activity of MC1R RHC variants. In a series of experiments in cultured cells, the authors found that protein palmitoylation (the addition of palmitic acid) to MC1R is essential for activating MC1R signalling, which ultimately triggers increased pigmentation. The authors also report that activating palmitoylation rescues the defects of MC1R RHC variants, increases pigmentation, and prevents the development of melanomas in MC1R RHC variant mice. They suggest that rescuing MC1R palmitoylation by up-regulation of the protein-acyl transferase ZDHHC13 or inhibition of depalmitoylation might prove to be the basis of potential clinical strategies to prevent melanomas in the future.