TSC2
小结
TSC2是抑癌基因，编码蛋白是tumerin，是mTOR信号传导途径的关键负调节物。mTOR信号传导途径在促进细胞生长和调节蛋白质合成中起重要作用。TSC2作为支架与TBC1D7和TSC1形成异聚复合物；TSC复合物起GTP酶活化蛋白（GAP）的作用并抑制RHEB，它是一种起小分子开关作用的GTP酶，当与GTP结合时激活mTORC1。TSC1和TSC2也被几种激酶（例如，AKT，RSK1，ERK，AMPK和GSK3）磷酸化，因此通过几种不同的信号传导途径提供对mTOR途径的调节抑制。TSC1中的胚系突变与结节性硬化症相关，结节性硬化症是导致良性和偶尔恶性肿瘤。在几种癌症（包括肝细胞癌）中检测到TSC1的体细胞突变，并且以截短功能丧失突变为主。
TSC2 (also tumerin) is a key negative regulator of the pro-oncogenic mTOR signaling pathway. The mTOR signaling pathway has a central role in promoting cellular growth and regulating protein synthesis. TSC2 acts as a scaffold to form a heteromeric complex with TBC1D7 and TSC1; the resulting TSC complex functions as a GTPase activating protein (GAP) and inhibits RHEB, which is a GTPase that functions as a small molecular switch, activating mTORC1 when bound to GTP. Both TSC1 and TSC2 are also phosphorylated by several kinases (e.g., AKT, RSK1, ERK, AMPK, and GSK3) thus providing regulatory inhibition of the mTOR pathway via several different signaling pathways. Both TSC1 and TSC2 are also phosphorylated by several kinases (e.g., AKT, RSK1, ERK, AMPK, and GSK3) thus providing regulatory inhibition of the mTOR pathway via several different signaling pathways. Germline mutations in TSC2 are associated with tuberous sclerosis, a disorder that results in benign and occasionally malignant tumor growths. Somatic TSC2 mutations have been identified in several cancers, including liver and endometrial cancers, and predominantly present as truncating loss-of-function mutations. TSC2 loss-of-function mutations result in constitutive activation of the mTORC1 complex resulting in sensitivity to mTOR-inhibiting agents (i.e., rapamycin analogs).