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Discovery of a new mechanism of gene control that is associated with cancer
Date:6/17/2011

This release is available in Spanish.

Researchers headed by Joan Massagu at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and by Mara Macas at the Institute for Research in Biomedicine (IRB Barcelona) have identified a complex mechanism by which some proteins that are essential for life, called Smads, regulate the activity of genes associated with cancer. The fruit of three years of intense work, the study reports on the life cycle of this protein, a process that ensures that the protein is destroyed when it has completed its function. These results have been published today in the top journal Genes & Development, which has devoted its cover to this research.

In the TGF-beta/Smad signal cascade, the hormones TGF-beta and BMP transmit information to the Smad protein in the cell nucleus in order for this molecule to stop cell division and to ensure that tissues grow in an orderly and coordinated manner. Although the TGF-beta/Smad signalling pathway has been known for over twenty years, until now it was unclear how Smads temporally controlled the activity of such important genes. "We had several pieces of the puzzle but we couldn't put them together", says Macas.

A number of earlier studies performed by Massagu's lab had identified that Smads undergo phosphorylations a kind of chemical change in a region of the protein about which little is known. By means of biophysical and biochemical approaches, the researchers have discovered that these modifications occur in a coordinated fashion over time and are not random. "First, phosphorylations make some proteins bind to Smads in order to control the activity of target genes and later other phoshorylations cause protein bindings that lead to the destruction of Smad once this protein has completed its mission. This is the way cells prevent fatal errors", explains Macas.

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Contact: Nuria Noriega
nuria.noriega@irbbarcelona.org
Institute for Research in Biomedicine (IRB Barcelona)
Source:Eurekalert

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