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Further experiments clinched the case for p53's role in tanning. When researchers inserted p53 into keratinocytes, POMC levels rose dramatically. When they delivered UV radiation to mice whose keratinocytes lacked p53, POMC production was not induced and the mice did not tan.
The implications of the research go beyond tanning. A variety of skin conditions are associated with the formation of dark spots that are unrelated to sun exposure. The spots arise when groups of cells begin producing pigment in response to repeated stress or irritation of the skin -- mimicking the tanning response. Although not dangerous, the condition can be a cosmetic problem, depending on its location.
"Our research offers a potential explanation of how this condition -- known as post-inflammatory hyperpigmentation -- occurs," Fisher says. "We know that it occurs as a result of stress, and p53 is a classic 'stress' protein, going into action when cells experience stress-related DNA damage. What we've learned about p53 suggests that it may trigger the hyperpigmentation process."
There is even the possibility that p53 protects against skin damage in a second -- and previously unsuspected -- way. The protein not only causes skin to tan in response to sunlight, it may also underlie people's desire to spend time in the sun. Spending time in the sun may be protective in people who tan easily.
The same process that causes POMC to produce a-MSH also leads to the production of b-endorphin, a natural opiate in the body that may be associated with feelings of pleasure. "Even as p53 causes skin to tan during sunlight exposure, it may also affect neuronal circuits," Fisher says. "These proteins may provide an explicit link between the regulation of tanning and of mood. It raises the question of whether p53-mediated induction of b-endorphin is involved in sun-seeking behavior, which often increases skin cancer risk."
The study's lead author is Rutao Cui, MD, PhD, of Dana-Farber and Children's Hospital Boston. Co-authors include Hans Widlund, PhD, Erez Feige, PhD, Jennifer Lin, MD, Dara Wilensky, Vivien Igras, and John D'Orazio, MD, PhD, formerly of Dana-Farber and Children's and now at the University of Kentucky College of Medicine; Scott Granter, MD, of Dana-Farber and Brigham and Women's Hospital; Claire Fung, MD, of Massachusetts General Hospital; and Carl Schanbacher, MD, of Brigham and Women's.
The research was supported by a grant from the National Institutes of Health, and the Doris Duke Charitable Foundation.
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