title: Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis.
abstract: The protein products of the tuberous sclerosis complex (TSC) genes, TSC1 and TSC2, form a complex, which inhibits the small G-protein, Ras homolog enriched in brain (Rheb). The vast majority of research regarding these proteins has focused on mammalian Target of Rapamycin (mTOR), a target of Rheb. Here, we propose that there are clinically relevant functions and targets of TSC1, TSC2 and Rheb, which are independent of mTOR. We present evidence that such non-canonical functions of the TSC-Rheb signalling network exist, propose a standard of evidence for these non-canonical functions, and discuss their potential clinical and therapeutic implications for patients with TSC and lymphangioleiomyomatosis (LAM).
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Neuman
authors.forename: Elizabeth Petri
authors.initials: EP
authors.lastname: Henske
mesh_terms: D000818:Animals; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins