Researchers identify LZTR1 as a component of the conserved RAS pathway during evolution

RAS mutations are responsible for the most aggressive tumors and the search for pharmacological inhibitors of these proteins has become a priority in the fight against cancer. Michail Steklov, Francesca Baietti, and colleagues from the Anna Sablina Laboratory (VIB-KU Leuven Cancer Biology Center) identified LZTR1 as a component of the conserved preservation RAS pathway.

Numerous genetic studies overwhelmingly emphasize the role of LZTR1 in a wide range of human disorders, such as Noonan Syndrome (a genetic disorder), liver cancer, childhood cancer and Schwannoma, a benign tumor affecting the nerves. The researchers found that LZTR1 contributed to human diseases by being part of the ubiquitin ligase complex that mediates ubiquitin conjugation to RAS proteins. This conjugation reduces the recruitment of RAS on the membrane and therefore its activation and downstream signaling.

Anna Sablina (VIB-KU Leuven): "Despite constant and exhaustive efforts to characterize RAS proteins, LZTR1 is the first new RAS regulator, implicated in human diseases, identified for years, and of course this will not be the case. possible without the help of our staff at UZ Leuven, the VIB-UGent Medical Biotechnology Center, the Frederick National Cancer Institute and the University of Alabama, and we hope that the discovery of this alternative regulatory mechanism RAS will lead to new approaches provoked diseases. "