Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome
Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome
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DOI：
10.1101/gad.1199104
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发表时间：
2004-07-01
影响因子：
10.5
通讯作者：
Guan, KL
中科院分区：
文献类型：
--
作者：
Corradetti, MN;Inoki, K;Guan, KL
结节性硬化症(TSC)和黑斑狼疮综合征(PJS)是主要的遗传性良性肿瘤综合征，在组织病理学上有显著的相似之处。在这里，我们证明了在PJS中突变的基因LKB1通过激活在TSC中突变的基因TSC2而发挥肿瘤抑制作用。与TSC2一样，LKB1抑制关键翻译调节因子S6K和4EBP1的磷酸化。此外，我们发现LKB1通过AMP依赖的蛋白激酶(AMPK)激活TSC2，表明LRB1在响应细胞能量水平的细胞生长调节中发挥作用。我们的结果提示，PJS和其他良性肿瘤综合征可能是由TSC2/mTOR通路调节失调引起的。
Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that LKB1, the gene mutated in PJS, acts as a tumor suppressor by activating TSC2, the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LRB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2/mTOR pathway.