| 背景 | Tuberin (TSC2) is a ~200 kDa protein. Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling. The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1. Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling. 1. Inoki, K. et al. (2002) Nature cell biology 4, 648-57. PMID: 121725532. Tee, AR. et al. (2002) Proceedings of the National Academy of Sciences of the United States of America 99, 13571-6. PMID: 122711413. Castro, AF. et al. (2003) The Journal of biological chemistry 278, 32493-6. PMID: 128428884. Tee, AR. et al. (2003) Current biology : CB 13, 1259-68. PMID: 129067855. Li, Y. et al. (2004) Molecular and cellular biology 24, 7965-75. PMID: 153400596. Mazhab-Jafari, MT. et al. (2012) Structure (London, England : 1993) 20, 1528-39. PMID: 228192198. Lim, JS. et al. (2017) American journal of human genetics 100, 454-472. PMID: 282154009. Yang, H. et al. (2021) Nature communications 12, 339. PMID: 3343662610. Ali, ES. et al. (2022) Molecular cell 82, 3284-3298.e7. PMID: 35772404 |
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