Nellist M, Goedbloed M A, Halley D J J
Department of Clinical Genetics, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Biochem Soc Trans. 2003 Jun;31(Pt 3):587-91. doi: 10.1042/bst0310587.
Tuberous sclerosis complex (TSC) is a genetic disorder characterized by seizures, mental disability, renal dysfunction and dermatological abnormalities. The disease is caused by inactivation of either hamartin or tuberin, the products of the TSC1 and TSC2 tumour-suppressor genes. Hamartin and tuberin form a complex and antagonise phosphoinositide 3-kinase/protein kinase B/target of rapamycin signal transduction by inhibiting p70 S6 kinase, an activator of translation, and activating 4E-binding protein 1, an inhibitor of translation initiation. Phosphorylation-dependent binding between tuberin and members of the 14-3-3 protein family indicates how the tuberin-hamartin complex may interact with upstream and downstream effectors, and suggests how phosphorylation-dependent regulation of the complex may be controlled.
结节性硬化症（TSC）是一种遗传性疾病，其特征为癫痫发作、智力残疾、肾功能障碍和皮肤异常。该疾病由TSC1和TSC2肿瘤抑制基因的产物错构瘤蛋白或结节蛋白失活引起。错构瘤蛋白和结节蛋白形成复合物，并通过抑制翻译激活因子p70 S6激酶和激活翻译起始抑制剂4E结合蛋白1来拮抗磷酸肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白信号转导。结节蛋白与14-3-3蛋白家族成员之间的磷酸化依赖性结合表明了结节蛋白-错构瘤蛋白复合物可能如何与上游和下游效应器相互作用，并提示了该复合物的磷酸化依赖性调节可能如何被控制。
