Cell
Volume 128, Issue 5, 9 March 2007, Pages 853-864
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Article
Central Role of p53 in the Suntan Response and Pathologic Hyperpigmentation

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Summary

UV-induced pigmentation (suntanning) requires induction of α-melanocyte-stimulating hormone (α-MSH) secretion by keratinocytes. α-MSH and other bioactive peptides are cleavage products of pro-opiomelanocortin (POMC). Here we provide biochemical and genetic evidence demonstrating that UV induction of POMC/MSH in skin is directly controlled by p53. Whereas p53 potently stimulates the POMC promoter in response to UV, the absence of p53, as in knockout mice, is associated with absence of the UV-tanning response. The same pathway produces β-endorphin, another POMC derivative, which potentially contributes to sun-seeking behaviors. Furthermore, several instances of UV-independent pathologic pigmentation are shown to involve p53 “mimicking” the tanning response. p53 thus functions as a sensor/effector for UV pigmentation, which is a nearly constant environmental exposure. Moreover, this pathway is activated in numerous conditions of pathologic pigmentation and thus mimics the tanning response.

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Present address: Pediatrics, The Markey Cancer Center, and The Graduate Center for Toxicology, University of Kentucky College of Medicine, Combs Research Building, 800 Rose Street, Speed Sort 0096, Lexington, KY 40536, USA.