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New findings on the genomic guardian

The p53 protein routinely shuts down damaged cells and is one of our main lines of defence against cancer. Scientists at Karolinska Institutet in Sweden now present new findings on how p53 carries out this all-important function.

The p53 transcription factor is found in every cell of the body, where it helps to prevent cancer by activating and deactivating the right genes. When the cell is exposed to potentially carcinogenic stress, such as DNA damage or oxygen deficiency, p53 can, for example, switch on the genetic programme for cell death, preventing the cancer from spreading to the rest of the body.

Almost half of all cancer tumours involve a mutation of the gene for p53, and in the hope of developing new cancer therapies, many cancer researchers study the mechanisms the protein controls.

Now, however, scientists at Karolinska Institutet have identified a great many of the proteins that are under the control of p53. Since p53 research has always been conducted at gene level, the study adds an entirely new dimension to our understanding of p53.

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“P53 can be likened to a conductor leading a cellular orchestra,” says Professor Klas Wiman, one of the scientists involved in the study. “Whereas we previously knew which instruments, or genes, make up the orchestra, we now have an idea of the music it plays, by which I mean the proteins that the genes express.”

The scientists have compared how the total protein configuration differs between cells with normally functioning p53 and cells lacking the protein. Their analyses show that p53 affects the expression of at least 115 other proteins, 55 of which have so far been identified.

“These proteins have an important part to play in cancer-related functions, such as apoptosis and metastasis, as well as in ageing,” says Professor Wiman. “Many of the mechanisms were previously unknown, and in several cases we can see changes at a protein level only, and not at a gene level. We believe this information to be of value to the development of new therapies.”

"P53 targets identified by protein expression profiling"
PNAS, online 19-23 March 2007, paper issue 27 March 2007

Katarina Sternudd | alfa
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