TSC2: filling the GAP in the mTOR signaling pathway
- PMID: 14729330
- DOI: 10.1016/j.tibs.2003.11.007
TSC2: filling the GAP in the mTOR signaling pathway
Abstract
The tumor-suppressor proteins TSC1 and TSC2 are associated with an autosomal dominant disorder known as tuberous sclerosis complex (TSC). TSC1 and TSC2 function as a heterodimer to inhibit cell growth and proliferation. Another protein, mTOR (mammalian target of rapamycin), is regarded as a central controller of cell growth in response to growth factors, cellular energy and nutrient levels. Recent breakthroughs in TSC research link the TSC1/2 heterodimer protein to the mTOR signaling network. It has recently been shown that TSC2 has GTPase-activating protein (GAP) activity towards the Ras family small GTPase Rheb (Ras homolog enriched in brain), and TSC1/2 antagonizes the mTOR signaling pathway via stimulation of GTP hydrolysis of Rheb. Thus, TSC1/2 and Rheb have pivotal roles in mediating growth factors, nutrient and energy sensing signals to mTOR-dependent targets. These discoveries lend new insight into TSC pathogenesis.
Similar articles
-
The mTOR/S6K signalling pathway: the role of the TSC1/2 tumour suppressor complex and the proto-oncogene Rheb.Novartis Found Symp. 2004;262:148-54; discussion 154-9, 265-8. Novartis Found Symp. 2004. PMID: 15562827 Review.
-
Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity.Mol Cell Biol. 2004 Sep;24(18):7965-75. doi: 10.1128/MCB.24.18.7965-7975.2004. Mol Cell Biol. 2004. PMID: 15340059 Free PMC article.
-
Rhebbing up mTOR: new insights on TSC1 and TSC2, and the pathogenesis of tuberous sclerosis.Cancer Biol Ther. 2003 Sep-Oct;2(5):471-6. doi: 10.4161/cbt.2.5.446. Cancer Biol Ther. 2003. PMID: 14614311 Review.
-
Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb.Curr Biol. 2003 Aug 5;13(15):1259-68. doi: 10.1016/s0960-9822(03)00506-2. Curr Biol. 2003. PMID: 12906785
-
Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.Genes Dev. 2003 Aug 1;17(15):1829-34. doi: 10.1101/gad.1110003. Epub 2003 Jul 17. Genes Dev. 2003. PMID: 12869586 Free PMC article.
Cited by
-
Tuberous sclerosis complex associated lymphangioleiomyomatosis caused by de novo mutation of TSC2 gene in Vietnam: A case report.Respirol Case Rep. 2024 Apr 9;12(4):e01346. doi: 10.1002/rcr2.1346. eCollection 2024 Apr. Respirol Case Rep. 2024. PMID: 38596252 Free PMC article.
-
MTOR modulation induces selective perturbations in histone methylation which influence the anti-proliferative effects of mTOR inhibitors.iScience. 2024 Feb 12;27(3):109188. doi: 10.1016/j.isci.2024.109188. eCollection 2024 Mar 15. iScience. 2024. PMID: 38433910 Free PMC article.
-
Early Post-Natal Immune Activation Leads to Object Memory Deficits in Female Tsc2+/- Mice: The Importance of Including Both Sexes in Neuroscience Research.Biomedicines. 2024 Jan 17;12(1):203. doi: 10.3390/biomedicines12010203. Biomedicines. 2024. PMID: 38255309 Free PMC article.
-
Mechanistic target of rapamycin in regulating macrophage function in inflammatory cardiovascular diseases.J Mol Cell Cardiol. 2024 Jan;186:111-124. doi: 10.1016/j.yjmcc.2023.10.011. Epub 2023 Nov 30. J Mol Cell Cardiol. 2024. PMID: 38039845 Free PMC article. Review.
-
Protective Role of Ethanol Extract of Cibotium barometz (Cibotium Rhizome) against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes.Int J Mol Sci. 2023 Sep 30;24(19):14798. doi: 10.3390/ijms241914798. Int J Mol Sci. 2023. PMID: 37834245 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous