Tuberous Sclerosis Complex and the Mammalian Target of Rapamycin Pathways
Published Online: 15 SEP 2010
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Yu, J. 2010. Tuberous Sclerosis Complex and the Mammalian Target of Rapamycin Pathways. eLS. .
- Published Online: 15 SEP 2010
Tuberous sclerosis complex (TSC) is an autosomal dominant disease in which the mammalian target of rapamycin complex 1 (mTORC1) is hyperactivated. Lymphangioleiomyomatosis (LAM) is the pulmonary manifestation of TSC which occurs primarily in women. The TSC proteins tuberin and hamartin regulate the small guanosine triphophatase (GTPase) Rheb (Ras homologue enriched in brain), a direct activator of mTORC1. Activation of mTORC1 has been observed in TSC tumours and other human tumours, and mTORC1 inhibitors have been tested for the treatment of TSC and for malignancies including renal cancer. In this article, we discuss diagnostic features, updated molecular basis, evidences of mTORC1 activation, preclinical models and completed clinical trials of mTORC1 inhibitors in TSC. We also review the evidence of mTORC1-independent functions of the TSC proteins, and discuss future therapeutic perspectives combining mTORC1 inhibitors with agents targeting other cellular pathways.
Tuberous sclerosis complex (TSC) is a hereditary disease characterised by the development of seizures, mental retardation, autism and hamartomas in multiple organs including the brain, retina, kidney, heart and skin.
Lymphangioleiomyomatosis (LAM) is the metastatic pulmonary manifestation of TSC occurring almost exclusively in women, in whom the lungs are infiltrated with abnormal smooth muscle-like cells and there is degeneration of lung parenchyma.
Metastasis is the multistep process in which tumour cells at the primary site spread to distant tissues/organs to proliferate.
Loss of heterozygosity refers to the loss of a normal allele on a chromosome while the other allele has a genetic alteration or mutation.
Mammalian target of rapamycin (mTOR) refers to the FRAP1 gene product, a serine/threonine protein kinase that controls ribosome biogenesis, protein translation, cell growth and metabolism.
- tuberous sclerosis complex;
- tumour suppressor;
- signal transduction