US scientists have found that the tumour suppressor gene p53 prompts skin to tan when exposed to sunlight and also may explain why people enjoy being in the sun.

The study is published in the journal Cell and is the work of scientists at Dana-Farber Cancer Institute, a principal teaching affiliate of the Harvard Medical School in Boston.

Scientists already knew the skin tans because it has special cells called keratinocytes that produce the dark pigment melanin and give it to other cells to shield them from DNA damage by ultraviolet (UV) light. But they did not know how UV light kickstarts melanin production in the first place.

The study’s lead author is Dr Rutao Cui, of Dana-Farber and Children’s Hospital. Another member of the team was Dr David Fisher, director of the Melanoma Program at Dana-Farber and a professor in pediatrics at Children’s Hospital Boston.

Dr Cui and colleagues suspected that the whole process starts when UV light triggers the gene p53 into action.

They tested this by exposing mice whose keratinocytes lacked p53 to UV light; their skin did not tan.

The researchers also explored the possibility that p53 protects the skin against DNA damage in another way – by triggering sun seeking behaviour. Apparently, when people are exposed to UV light, like that of the sun, p53 triggers a process that releases a hormone, b-endorphin, that docks in opiate receptors in brain cells and is linked to feelings of pleasure.

According to Dr Fisher, “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.”

He said that this research shows that p53 “has a powerful role in protecting us against sun damage in the skin.”

The discovery, in retrospect, was not a surprise since p53 is one of the best-known tumour suppressors and DNA damage protectors in the body. It has been nicknamed the “master watchman of the genome”.

This dual pigmentation triggering and tumour suppressing role of p53 might also explain another phenomenon – age spots. These are dark patches on the skin that mostly appear when people get older. They result from stress of some kind, not necessarily sun exposure.

P53 is activated whenever the skin is stressed, for example by chemotherapy, and since this threatens DNA health, p53 kicks in with its protective role, triggering melanin production and delivery to cells that don’t “know that it isn’t sunshine that induced p53,” says Dr Fisher.

The researchers were able to reveal exactly what happens inside skin cells when UV light shines on them to when the tanning begins.

They already knew that when UV light falls on skin cells it stimulates the keratinocytes to make and release a hormone called alpha-MSH. This hormone sticks to another type of cell that is nearby called melanocytes, and causes them to produce melanin.

Previous studies have also revealed that alpha-MSH is a byproduct of the break up of another protein, pro-opiomelanocortin (or POMC), and that POMC levels rise when cells are exposed to UV light. But the underlying process was still a mystery until this study.

This study suggests the key lies with p53 and its interaction with POMC. Dr Fisher and colleagues looked at the gene that codes for POMC protein and they found a section of it was a docking “port” that fit p53 exactly. They had a hunch that when p53 docks on the gene for POMC it revs up POMC production.

They verified their hunch with experiments on mouse and human cells.

When they exposed mouse and human keratinocytes to 6 hours of UV radiation, in both cases POMC and p53 levels shot up way above normal, and the pigment stimulating protein alpha-MSH was present at 30 times above the normal level.

“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, and David E. Fisher.
Cell, Vol 128, 853-864, 09 March 2007

Click here for Abstract.

Written by: Catharine Paddock
Writer: Medical News Today