News
The intimate bond between three proteins linked to cancer now unveiled
Published on février 12, 2018
The team of Marc Therrien, Scientific Director and Principal Investigator at IRIC, proposes a true paradigm shift in an article published in the prestigious scientific journal Nature.
Professor Therrien’s group was interested in the mechanism of activation of BRAF, a protein involved in many cancers because of its role as an activator of MEK. Together, these two proteins stimulate cellular growth and division.
Up to now, there was an agreement on a model in which BRAF was brought to encounter MEK, with the help of a “matchmaker” protein, KSR guiding the two partners towards each other and leading BRAF to activate MEK.
But it now seems that KSR doesn’t only have a passive role in the story…
To show this, the IRIC researchers first analyzed, at a molecular level, how BRAF and KSR associate. They then discovered that KSR activated BRAF but only if MEK bound to KSR, beforehand.
You’re scratching your head? The researchers did too when they discovered this new mechanism. They had just revealed that MEK, a protein perceived until then as the ultimate target of the process, also acted as an indirect stimulator of BRAF, by attaching itself to KSR. According to them, such a mechanism would then drive BRAF to become hyperactive and stimulate, in turn, every MEK protein in close proximity.
Such a signal amplification mechanism between an activated protein and its activator has already been observed in other situations. However, it was not suspected in this case.
As a whole, this finding from the IRIC researchers is a major contribution. It not only proposes a new way to see how these important proteins interact with each other, but also reveals a new therapeutic target. According to them, preventing the binding of BRAF and KSR using small molecules is likely to slow down the progression of certain cancers.
To read the full article: https://www.nature.com/articles/nature25478
By Martin Primeau