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

doi:10.1016/j.cell.2006.12.045

Central role of p53 in the suntan response and pathologic hyperpigmentation

Cell. 2007 Mar 9;128(5):853-64. doi: 10.1016/j.cell.2006.12.045.

Authors

Rutao Cui¹, 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

Affiliation

¹ Melanoma Program in Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

PMID: 17350573
DOI: 10.1016/j.cell.2006.12.045

Abstract

UV-induced pigmentation (suntanning) requires induction of alpha-melanocyte-stimulating hormone (alpha-MSH) secretion by keratinocytes. alpha-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 beta-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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Carcinoma, Basal Cell / genetics
Carcinoma, Basal Cell / metabolism
Cell Culture Techniques
Cell Line, Tumor
Foreskin / metabolism
Foreskin / pathology
Genes, p53*
Humans
Hyperpigmentation / metabolism*
Keratinocytes / cytology
Keratinocytes / metabolism
Keratinocytes / radiation effects
Male
Melanocytes / metabolism
Melanocytes / radiation effects
Mice
Mice, Inbred C57BL
Mice, Knockout
Pro-Opiomelanocortin / genetics
Promoter Regions, Genetic
RNA, Messenger / genetics
RNA, Messenger / metabolism
Skin / metabolism*
Skin / radiation effects
Skin Neoplasms / genetics
Skin Neoplasms / metabolism
Skin Pigmentation*
Transcriptional Activation*
Tumor Suppressor Protein p53 / metabolism
Ultraviolet Rays / adverse effects*
Up-Regulation
alpha-MSH / metabolism
beta-Endorphin / metabolism

Substances

RNA, Messenger
Tumor Suppressor Protein p53
alpha-MSH
beta-Endorphin
Pro-Opiomelanocortin