Abstract
Evaluation of: McGowan KA, Li JZ, Park CY et al. Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects. Nat. Genet. 40(8), 963–970 (2008).
Melanocytes (MCs) sit along the epidermal basal layer, largely quiescent except for constitutive melanin production. They are usually only activated following sun exposure. The recent paper by McGowan et al. describes a novel mechanism by which MCs are induced to proliferate upon p53 activation in adjacent keratinocytes. In this study, small subunit ribosomal protein mutations cause a dramatic activation of p53, which we propose mimics important aspects of the skin sunburn response after UV radiation exposure. McGowan et al. show that the phenotype of their hyperpigmented mouse mutants results from p53-dependent upregulation of KIT ligand, a cytokine that binds to the KIT receptor on MCs and influences melanin synthesis, MC proliferation and dictates MC localization at the dermo–epidermal junction. These findings extend our knowledge about skin stress responses – in particular, how p53 activity in keratinocytes is central to the regulation of MC behavior.
Financial & competing interests disclosure
The authors work was supported by the Cancer Council of Queensland (G Walker), the Dermatology Foundation (N Box) and the American Skin Association (N Box). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.