Scientists discover how rapamycin slows cell growth

“Cells normally monitor the availability of nutrients and will slow down or accelerate their growth and division accordingly. A key monitor of nutrients is a protein called the Target of Rapamycin (TOR), but we do not know the details of how this protein feeds signals downstream to control growth” says Dr. Stephen Michnick, senior author and a University of Montreal biochemistry professor. He adds that, “we were surprised to find that TOR hooks up to a circuit that controls the exit of cells from division which in turn modulates the RNA message that codes for a key cell cycle regulator called B-cyclin”.

In collaboration with Daniel Zenklusen, also a University of Montreal biochemistry professor and lead author and doctoral candidate Vincent Messier, they discovered that when cells are starved for nutrients TOR sends a signal to shut down production of a chemical message in the form of RNA to synthesize B cyclin ”, Dr. Michnick explained. “We also found that TOR acts through a previously unforeseen intermediary, a protein that makes small chemical modifications to proteins normally stabilizing B cyclin RNA ”, he added. “We have known that starvation and a drug that mimics starvation, rapamycin, affects B cyclin synthesis, but we didn't know how. Our studies now point to one mechanism”, noted Dr. Messier. Dr. Zenklusen emphasized that, “this is an important finding with implications for our understanding on how the normal organism interprets its environment to control growth and it was a surprise to find a mechanism that works through the RNA that codes for a regulatory protein”.
Dr. Michnick adds, “rapamycin is a promising therapy for some cancers and other devastating maladies such as the rare lung disease called lymphangioleiomyomatosis (LAM). It remains to be seen whether the pathway we have discovered might be an alternative target for the development of therapeutics against these diseases.”

Notes:
The University of Montreal is known officially as Université de Montréal. The research involved in the study “A Nutrient-Responsive Pathway that Determines M Phase Timing through Control of B-Cyclin mRNA Stability” was financed by Canadian Institutes of Health Research (CIHR) grants MOP-GMX-152556 and MOP-GMX- 231013 and NSERC of Canada grant 194582 to Dr. Michnick and CIHR grant MOP-BMB-232642 and the Canadian Foundation for Innovation to Dr. Zenklusen. Dr. Zenklusen holds a FRSQ Chercheur Boursier Junior I.
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