The protein mTOR is a central player in many human diseases, including cancer and cardiovascular dysfunction, and is the target for major efforts in drug discovery in the pharmaceutical industry. Much is known about signaling mechanisms leading to activation of mTOR, but mechanisms controlling protein turnover are currently unknown. Mao et al. demonstrated that FBXW7, a tumor suppressor protein recently identified as another major target for mutation or loss in human cancers, interacts with and targets mTOR for degradation through the proteasome pathway. Because FBXW7 is a haploinsufficient human tumor suppressor gene, the data provide insights into the control of mTOR signaling and suggest possible strategies for therapeutic intervention.
J.-H. Mao, I.-J. Kim, D. Wu, J. Climent, H. C. Kang, R. DelRosario, A. Balmain, FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science 321, 1499-1502 (2008). [Abstract] [Full Text]