Regulation of TS1/TSC2 Stability and Rheb GTP Level by Herc1

摘要: Abstract : Over the past decade, considerable progress has been made in understanding molecular genetics of Tuberous Sclerosis (TSC), highlighted by identification two tumor suppressor genes tsc1 and tsc2. Mutations either or tsc2 cause disease TSC. A surge recent research from several labs shown that TSC1/2 antagonizes mTOR (mammalian target rapamycin) signaling network, which plays a central role regulation cell growth response to factors, cellular energy, nutrient levels. In TSC1 TSC2 mutant cells, pathway, as determined phosphorylation S6K (ribosomal S6 kinase) 4EBP1 (eukaryote initiation factor 4E binding protein), is highly elevated. Recent studies have also functions GTPase activating protein (GAP) stimulate GTP hydrolysis Rheb (a Ras family GTPase), therefore, inactivating Rheb. Both genetic biochemical support key direct downstream an essential mediate physiological TSC1/TSC2. The main objective this project investigate function Herc TSC1/TSC2 stability level.