Journal
BIOCHEMICAL JOURNAL
Volume 412, Issue -, Pages 179-190Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20080281
Keywords
cell growth control; hamartin (TSC1); mammalian target of rapamycin complex 1 (mTORC1); Ras homologue enriched in brain (Rheb); tuberin (TSC2); tuberous sclerosis complex (TSC)
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Funding
- NCI NIH HHS [P01 CA120964, R01-CA122617, P01 CA120964-02, P01-CA120964, R01 CA122617, R01 CA122617-02] Funding Source: Medline
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TSC1 and TSC2 are the tumour-suppressor genes mutated in the tumour syndrome TSC (tuberous sclerosis complex). Their gene products form a complex that has become the focus of many signal transduction researchers. The TSC1-TSC2 (hamartin-tuberin) complex, through its GAP (GTPase-activating protein) activity towards the small G-protein Rheb (Ras homologue enriched in brain), is a critical negative regulator of mTORC1 (mammalian target of rapamycin complex 1). As mTORC1 activity controls anabolic processes to promote cell growth, it is exquisitely sensitive to alterations in cell growth conditions. Through numerous phosphorylation events, the TSC1-TSC2 complex has emerged as the sensor and integrator of these growth conditions, relaying signals from diverse cellular pathways to properly modulate mTORC1 activity. In the present review we focus on the molecular details of TSC1-TSC2 complex regulation and function as it relates to the control of Rheb and mTORC1.
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