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Manuel Serrano

01/10/2009
Science Signaling: New advances on p53

Madrid, October 2009. Scientists at the CNIO have uncovered a new mechanism of how the tumour suppressor protein p53 is regulated. Their findings have been published in the prestigious journal Science Signaling.

The researchers Susana Llanos and Manuel Serrano, from the CNIO's Tumour Suppression Group, have found an unexpected relationship between the proteins p53 and MSK2. They observed that MSK2 inhibits p53, thus preventing cell suicide. These results may help to better understand how some cancer cells become insensitive to p53 control.

p53

The protein p53 is one of the most intensively investigated proteins our genome encodes. The reason that scientists are so interested in a single protein is because p53 detects whether or not a cell is working correctly. Practically all alterations a cell can undergo are relayed through molecular pathways that converge on p53 which, after integration of the information, "decides" if the cell should be kept on functioning or has been damaged so badly that it ought to be eliminated. This "suicide function" of p53 ensures that non-functional cells are duly eliminated from our tissues, something that would otherwise pose an evident risk. In fact, accidental mutations in and loss of p53 are responsible for nearly 50% of human cancers while in the other 50% of cancers p53 function is usually impaired in one way or another.

MSK2: one of the "surveyors" of p53

The work recently published in the journal Science Signaling goes back to three years ago when the researcher Susana Llanos searched through a total of 8,000 proteins to find some that could inhibit p53, but had not been previously related to p53. In other words, Susana was looking for new "surveyors" that would transmit to p53 the message that everything was fine and the cell does not have to commit suicide. In this search she found MSK2 and after three years of detailed studies she has been able to uncover the mechanism by which MSK2 inhibits p53. "The novelty of Susana’s findings is that MSK2 halts p300, one of the executing arms of p53, and this mechanism of action on p53 was totally unknown and unprecedented" - says Manuel Serrano.

Better understanding of chemotherapy and of p53

According to the model put forward by the authors, MSK2 is one of the proteins that "report" to p53 that everything inside the cell is sound. As soon as the cells get damaged, however, e.g. after ultraviolet irradiation or exposure to a chemotherapy agent, MSK2 vanishes and p53 induces cell suicide. The researchers note that their results are still far from being translated into practical applications, but insist on the importance of understanding how p53 is constantly on the "watch" for abnormal or cancer cells that ought to be eliminated from our bodies.