Discovery of New Element in Class of Enzymes Informs Cancer Drug Design

The enzyme mTORC2 has been an enigmatic regulator of other enzymes (kinases) such as Protein Kinase C (PKC) and Akt. Now researchers at University of California San Diego School of Medicine have solved the mystery to what mTORC2 does, opening avenues to selectively target its function. They discovered that all kinases regulated by mTORC2 have a newly discovered motif now known as the TOR Interaction Motif. Using PKC as an example, the researchers showed that mTORC2 adds a phosphate group on this motif, which is important for PKC to mature into a functional enzyme. This is important information because while Akt promotes tumors, PKC suppresses them. Inhibiting mTORC2 — the basis of several anti-cancer drugs currently in development — might turn PKC “off,” and thus might promote tumors instead of suppressing them. By understanding what mTORC2 does, approaches to protect PKC from mTOR inhibitors can now be designed. The study is published April 13, 2021 in Science Signaling: https://stke.sciencemag.org/content/14/678/eabe4509