Non‐canonical functions of the tuberous sclerosis complex‐Rheb signalling axis

• Published in: EMBO molecular medicine Vol. 3; no. 4; pp. 189 - 200
• Main Authors: Neuman, Nicole A., Henske, Elizabeth Petri
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2011; WILEY‐VCH Verlag; EMBO Press; WILEY-VCH Verlag
• Subjects: Animal cognition; Animals; Autism; Cell growth; Disease; Humans; In Focus; Kinases; Lungs; lymphangioleiomyomatosis; Monomeric GTP-Binding Proteins - genetics; Monomeric GTP-Binding Proteins - metabolism; mTOR; Neuropeptides - genetics; Neuropeptides - metabolism; non‐canonical; Proteins; Rapamycin; Ras Homolog Enriched in Brain Protein; Rheb; Signal Transduction; Smooth muscle; TOR protein; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Tuberous sclerosis; Tuberous Sclerosis - genetics; Tuberous Sclerosis - metabolism; tuberous sclerosis complex; Tuberous Sclerosis Complex 1; Tuberous Sclerosis Complex 2; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; mTOR; non‐canonical; tuberous sclerosis complex; Rheb; lymphangioleiomyomatosis
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.1002/emmm.201100131

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).