Ribosomal stress, p53 activation and the tanning response

Melanocytes (MC) sit along the epidermal basal layer, largely quiescent except for constitutive melanin production. They are usually only activated after sun exposure. The recent paper by McGowan et al. (1) describes a novel mechanism by which melanocytes are induced to proliferate upon p53 activation in adjacent keratinocytes (KC). In this study, small subunit ribosomal protein mutations cause a dramatic activation of p53 that we propose mimics important aspects of the skin sunburn response after ultraviolet radiation (UVR) exposure. McGowan et al. show that the phenotype of their hyperpigmented mouse mutants results from p53-dependent upregulation of KITLG, a cytokine that binds to the KIT receptor on melanocytes and influences melanin synthesis, melanocyte 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 melanocyte behaviour.