'Guardian of the Genome' Protein Found to Underlie Skin Tanning

Mar 08, 2007

A protein known as the “master watchman of the genome” for its ability to guard against cancer-causing DNA damage has been found to provide an entirely different level of cancer protection: By prompting the skin to tan in response to ultraviolet light from the sun, it deters the development of melanoma skin cancer, the fastest-increasing form of cancer in the world.

In a study in the March 9 issue of the journal Cell, researchers at Dana-Farber Cancer Institute report that the protein, p53, is not only linked to skin tanning, but also may play a role in people’s seemingly universal desire to be in the sun – an activity that, by promoting tanning, can reduce one’s risk of melanoma.

“The number one risk factor for melanoma is an inability to tan; people who tan easily or have dark pigmentation are far less likely to develop the disease,” says the study’s senior author, David E. Fisher, MD, PhD, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children's Hospital Boston. “This study suggests that p53, one of the best-known tumor-suppressor proteins in our body, has a powerful role in protecting us against sun damage in the skin.”

In a study published last year, Fisher and his colleagues found that ultraviolet (UV) radiation from the sun causes skin cells called keratinocytes to make and secrete a hormone called α-MSH, which attaches to nearby skin cells called melanocytes and spurs them to produce skin-darkening pigment called melanin. The chain of events within keratinocytes that leads to &alph-MSH production, however, was a mystery.

Investigators knew that α-MSH is created when another protein, known as pro-opiomelanocortin (or POMC), is split apart. They also knew that the amount of POMC within cells rises sharply when they’re exposed to UV rays. But they didn’t know what caused the POMC to increase.

One possibility was p53. When Fisher and his colleagues examined the section of the 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 α-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 α-MSH also leads to the production of β-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 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 β-endorphin is involved in sun-seeking behavior, which often increases skin cancer risk.”

Source: Dana-Farber Cancer Institute

Explore further: A novel therapy for sepsis?

add to favorites email to friend print save as pdf

Related Stories

US judge fines HP $59 mn for bribing Russian officials

4 hours ago

A judge on Thursday ordered US computer giant Hewlett-Packard to pay $58.8 million for bribing Russian government officials to win a big-money contract with the prosecutor general's office in that nation.

Solar storm heads Earth's way after double sun blasts

4 hours ago

Two big explosions on the surface of the sun will cause a moderate to strong geomagnetic storm on Earth in the coming days, possibly disrupting radio and satellite communications, scientists said Thursday.

US threatened Yahoo with huge fine over surveillance

5 hours ago

US authorities threatened to fine Yahoo $250,000 a day if it failed to comply with a secret surveillance program requiring it to hand over user data in the name of national security, court documents showed ...

Microbes evolve faster than ocean can disperse them

5 hours ago

Two Northeastern University researchers and their international colleagues have created an advanced model aimed at exploring the role of neutral evolution in the biogeographic distribution of ocean microbes.

Recommended for you

A novel therapy for sepsis?

14 hours ago

A University of Tokyo research group has discovered that pentatraxin 3 (PTX3), a protein that helps the innate immune system target invaders such as bacteria and viruses, can reduce mortality of mice suffering ...

Cellular protein may be key to longevity

Sep 15, 2014

Researchers have found that levels of a regulatory protein called ATF4, and the corresponding levels of the molecules whose expression it controls, are elevated in the livers of mice exposed to multiple interventions ...

Gut bacteria tire out T cells

Sep 15, 2014

Leaky intestines may cripple bacteria-fighting immune cells in patients with a rare hereditary disease, according to a study by researchers in Lausanne, Switzerland. The study, published in The Journal of Experimental Me ...

User comments : 0