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'Guardian of the genome' protein found to underlie skin tanning

e gene for POMC that promotes production of the protein, they found it meshed nicely with p53 ?suggesting that when p53 docks there, it revs up POMC production. Additional evidence came when the researchers exposed human and mouse keratinocytes to UV radiation: After six hours, levels of both POMC and p53 were far higher than normal, and the level of pigment-stimulating alpha-MSH was 30 times above normal.

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 common skin condition, especially among the elderly, is the development of small, 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. 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, or age spots ?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.

The same process that causes POMC to produce alpha-MSH also leads to the production of b-endorphin, a protein that binds to the body's opiate receptors and may be associated with feelings of pleasure. "Even as p53 is causing skin to t
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Source:Dana-Farber Cancer Institute


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