A complex mechanism by which some proteins that are essential for life, called Smads, regulate the activity of genes associated with cancer has been identified by scientists.
The study headed by Joan Massague at Memorial Sloan-Kettering Cancer Center, New York, and by Maria Macias at the Institute for Research in Biomedicine, Barcelona, reports on the life cycle of this protein, a process that ensures that the protein is destroyed when it has completed its function.
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.
A number of earlier studies performed by Massague's lab had identified that Smads undergo phosphorylations -a kind of chemical change - in a region of the protein about which little is known.
Now, 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", described Macias.
About how these proteins favour tumour cells, Massague explained, "these signalling cascades are like the body's police force. The tumour cells, in other words the delinquents, disturb these pathways and use them for their own means to grow and spread".
These pathways normally are involved in basic cell processes but when altered by mutations several diseases can appear such as cancer, congenital conditions, chronic inflammation and emphysema.
These results could serve as the foundation on which to develop new clinical treatments against cancer and other diseases.
The study has been published in the top journal Genes and Development.