TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone Hsp90 (heat shock protein-90) and decelerates its chaperone cycle. Tsc1 functions as a facilitator of Hsp90 in chaperoning the kinase and non-kinase clients including Tsc2, therefore preventing their ubiquitination and degradation in the proteasome.[6] TSC1, TSC2 and TBC1D7 is a multi-protein complex also known as the TSC complex. This complex negatively regulates mTORC1 signaling by functioning as a GTPase-activating protein (GAP) for the small GTPase Rheb, an essential activator of mTORC1. The TSC complex has been implicated as a tumor suppressor.
Clinical significance[]
Defects in this gene can cause tuberous sclerosis, due to a functional impairment of the TSC complex.[citation needed] Defects in TSC1 may also be a cause of focal cortical dysplasia.[citation needed] TSC1 may be involved in protecting brain neurons in the CA3 region of the hippocampus from the effects of stroke.[7]
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^Murthy V, Haddad LA, Smith N, Pinney D, Tyszkowski R, Brown D, Ramesh V (May 2000). "Similarities and differences in the subcellular localization of hamartin and tuberin in the kidney". American Journal of Physiology. Renal Physiology. 278 (5): F737–46. doi:10.1152/ajprenal.2000.278.5.F737. PMID10807585.
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Ramesh V (June 2003). "Aspects of tuberous sclerosis complex (TSC) protein function in the brain". Biochemical Society Transactions. 31 (Pt 3): 579–83. doi:10.1042/BST0310579. PMID12773159.
Knowles MA, Hornigold N, Pitt E (June 2003). "Tuberous sclerosis complex (TSC) gene involvement in sporadic tumours". Biochemical Society Transactions. 31 (Pt 3): 597–602. doi:10.1042/BST0310597. PMID12773163.
Jozwiak J, Jozwiak S (March 2007). "Giant cells: contradiction to two-hit model of tuber formation?". Cellular and Molecular Neurobiology. 27 (2): 251–61. doi:10.1007/s10571-006-9106-0. PMID16897363. S2CID31624726.
Plank TL, Yeung RS, Henske EP (November 1998). "Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles". Cancer Research. 58 (21): 4766–70. PMID9809973.
Niida Y, Lawrence-Smith N, Banwell A, Hammer E, Lewis J, Beauchamp RL, Sims K, Ramesh V, Ozelius L (2000). "Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis". Human Mutation. 14 (5): 412–22. doi:10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K. PMID10533067.
Yamashita Y, Ono J, Okada S, Wataya-Kaneda M, Yoshikawa K, Nishizawa M, Hirayama Y, Kobayashi E, Seyama K, Hino O (January 2000). "Analysis of all exons of TSC1 and TSC2 genes for germline mutations in Japanese patients with tuberous sclerosis: report of 10 mutations". American Journal of Medical Genetics. 90 (2): 123–6. doi:10.1002/(SICI)1096-8628(20000117)90:2<123::AID-AJMG7>3.0.CO;2-L. PMID10607950.
Lamb RF, Roy C, Diefenbach TJ, Vinters HV, Johnson MW, Jay DG, Hall A (May 2000). "The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho". Nature Cell Biology. 2 (5): 281–7. doi:10.1038/35010550. PMID10806479. S2CID25353057.
Murthy V, Stemmer-Rachamimov AO, Haddad LA, Roy JE, Cutone AN, Beauchamp RL, Smith N, Louis DN, Ramesh V (March 2001). "Developmental expression of the tuberous sclerosis proteins tuberin and hamartin". Acta Neuropathologica. 101 (3): 202–10. doi:10.1007/s004010000269. PMID11307618. S2CID8067136.