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Discovery could lead to more effective cancer treatments September 10 - Molecular Genetics professor Dr. Frank Sicheri, based in the Samule Lunenfeld Research Insituted, has co-authored a paper showing how protein molecules called RAF tell cells to grow, a discovery that could potentially lead to more effective chemotherapy drugs with fewer side effects.f The discovery is outlined in an article published in the scientific journal Nature, and co-authored by Dr. Sicheri and Dr. Marc Therrien of the Institute for Research in Immunology and Cancer at the Université de Montréal. The authors show that a type of protein called RAF - from a family of proteins known as kinase function as a signaling pathway that tells cells to grow. “When functioning normally, the pathway also signals that cells should eventually stop growing,” says Thanashan Rajakulendran, a PhD candidate in Dr. Sicheri’s lab who worked on the project. “But with cancer, RAF molecules act as a messenger that tells cells to keep growing indefinitely.” The researchers have discovered that RAF molecules must come into contact with one another in order to switch on the signaling pathway that causes cell growth. Currently, cancer drugs don’t just target RAF molecules, but also affect other proteins from the kinase family. That can lead to the toxicity and side effects of chemotherapy. The discovery could lead to potentially developing drugs that can bind to RAF molecules. This would lead to shutting down unchecked growth so that cancer cells die, as well as eliminating the unwanted side effects of current chemotherapy treatment. “Protein kinases are the targets for some of the most successful anti-cancer drugs in the clinic,” says Dr. Sicheri. “Now that we have discovered how to turn off the RAF protein without interfering with other proteins, we may be able to design drugs that have unprecedented precision in targeting cancer cells while reducing the toxic side effects for patients.”

Focus on Research Archives: How our genes remember (or forget) their past experience. More U of T researchers identify proteincontrolling brain formation. More U of T researchers discover new way to fight drug resistant fungal infections. More U of T researchers find switching off protein “thermostat” shuts down deadly fungal disease. More The Hsp90-Antifungal Combo, Please: Compromising Fungi in the Immunocompromised. More Looking Ahead in Cancer Stem Cell Research. More Global Map of SUMO Function revealed by Protein-Protein and Genetic Networks. More The DNA-encoded nucleosome organization of a eukaryotic genome. More A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. More Researchers Reveal Epstein-Barr Virus Protein Contributes to Cancer. More Scientists validate the formation of cruciform structures in eukaryotic DNA and identify a cruciform cleaving nuclease. More Scientists in the Department of Molecular Genetics have established that, despite our many differences, the genes that control the development of eyes in humans and flies are remarkably conserved. More In a study published in Molecular Biology of the Cell in September, Dr Wilde’s group defines a signaling pathway from mitotic chromosomes to the cell surface. More Dr. Lori Fappier's research team along with Affinium Pharmaceutical Inc., identify herpesvirus proteins that target key cellular processes. More Guri Giaever's research team demonstrated that nearly all (97%) yeast genes, when deleted, manifest a significant growth phenotype in at least one experimental condition. More Research from the Blencowe lab reveals that humans and chimpanzees differ at the level of alternative splicing .More Igor Stagljar's group developed a novel method for the elucidation of protein-protein interactions called Cross-and Capture. More In a paper in the upcoming issue of Nature Genetics, Corey Nislow's group from the University of Toronto in collaboration with Ron Davis and William Lee at Stanford, has provided a complete, 3-D map of the yeast genome, a Google Earth-like view of the position of all 70,000 nucleosomes in the genome. More Dr. John Roder and colleagues demonstrated for the first time that malfunction of a gene that had been associated with schizophrenia and depression does indeed cause symptoms of those disorders. More Cancer researchers led by Dr. John Dick have developed a method to convert normal human blood cells into “human” leukemia stem cells. More The Stagljar lab developed a unique assay called integrated membrane yeast-two hybrid (iMYTH) that identifies protein-interactors of transmembrane proteins such as the ABC transporters. More