Roles of Tuberous Sclerosis Complex Proteins in Autophagy and Cell Death

Abstract

Despite the cells deficient of tuberous sclerosis complex proteins are known to be susceptible to various stress factors, the function of these proteins in cell stress responses has not been fully understood. We have therefore studied the functional roles of TSC in autophagy and cell death under starvation and oxidative stress, respectively. We first found that the lower autophagy level contributes to the sensitivity of these cells to various death stimuli. We next studied the role of TSC in JNK signaling under oxidative stress. Initial findings found that the JNK activation is impaired in TSC deficient cells. Subsequently, a novel function of TSC is found; TSC interacts with mitogen activated protein kinase phosphatase 1. In addition, the impaired JNK activation promoted necroptosis in response to oxidative stress. Taken together, we conclude that TSC is an important modulator in autophagy and cell death.