11 - TOR Signaling and Cell Death

Abstract

Publisher Summary This chapter discusses the target of rapamycin (TOR) signaling and cell death. The evolutionarily conserved serine/threonine protein kinase, TOR, acts as a central effector of cell growth by controlling diverse metabolic processes, including translation initiation, ribosome biosynthesis, lipid synthesis, endocytosis, nutrient uptake, cytoskeleton organization, and autophagy. In metazoans, the coupling of cell growth and cell death together controls tissue homeostasis. As a growth regulator, TOR signaling affects cell death, in a bidirectional manner. Consistent with its cell growth functions, the TOR pathway has a cell-protective role that counteracts multiple cell death signals. Hyperactive TOR signaling can also enhance the induction of cell death by various signals. The inhibition of TOR signaling can protect cells against a variety of insults that promote cell death—especially in neuronal degeneration disorders. Therefore, manipulation of the TOR pathway or its downstream targets has emerged as a promising approach for the therapy of diseases, including cancers and neurodegenerative diseases. The chapter summarizes recent findings regarding the modification of cell death signals by TOR signaling, suggests possible mechanisms, and explores the potential implications of these findings for disease therapy.