Central Role of p53 in the Suntan Response and Pathologic Hyperpigmentation

Rutao Cui, Hans R. Widlund, Erez Feige, Jennifer Y. Lin, Dara L. Wilensky, Viven E. Igras, John D'Orazio, Claire Y. Fung, Carl F. Schanbacher, Scott R. Granter, David E. Fisher

Research output: Contribution to journalArticlepeer-review

508 Scopus citations


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.

Original languageEnglish
Pages (from-to)853-864
Number of pages12
Issue number5
StatePublished - Mar 9 2007

Bibliographical note

Funding Information:
We thank members of the Fisher lab for their encouragement and comments. We thank all members of the Benz-Huang lab for their generous help with the Stratalinker UV chamber and Dr. Stuart Yuspa for PAM212 cells. This work was supported by a grant from the National Institutes of Health (D.E.F.). D.E.F. is the Jan and Charles Nirenberg Fellow in Pediatric Oncology and Distinguished Clinical Scholar of the Doris Duke Charitable Foundation. D.E.F. discloses an equity and consulting relationship with Magen Biosciences.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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