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首页> 外文期刊>Cellular Signalling >Tumour suppressors hamartin and tuberin: intracellular signalling [Review]
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Tumour suppressors hamartin and tuberin: intracellular signalling [Review]

机译：肿瘤抑制因子ha玛汀和管蛋白：细胞内信号传导[综述]

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摘要

Tumour suppressors hamartin and tuberin, encoded by tuberous sclerosis complex 1(TSC1) and TSC2 genes, respectively, are critical regulators of cell growth and proliferation. Mutations in TSC1 and TSC2 genes are the cause of an autosomal dominant disorder known as tuberous sclerosis complex (TSC). Another genetic disorder, lymphangioleiomyomatosis (LAM), is also associated with mutations in the TSC2 gene. Hamartin and tuberin control cell growth by negatively regulating S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), potentially through their upstream modulator mammalian target of rapamycin (mTOR). Growth factors and insulin promote Akt/PKB-dependent phosphorylation of tuberin, which in turn, releases S6K1 from negative regulation by tuberin and results in the activation of S6K1. Although much has been written regarding the molecular genetics of TSC and LAM, which is associated with either the loss of or mutation in the TSC1 and TSC2 genes, few reviews have addressed the intracellular signalling pathways regulated by hamartin and tuberin. The current review will fill the gap in our understanding of their role in cellular signalling networks, and by improving this understanding, an integrated picture regarding the normal function of tuberin and hamartin is beginning to emerge. (C) 2003 Elsevier Science Inc. All rights reserved. [References: 127]
机译：肿瘤抑制因子martin和tuberin分别由结节性硬化复合物1（TSC1）和TSC2基因编码，是细胞生长和增殖的关键调节剂。 TSC1和TSC2基因中的突变是常染色体显性遗传病（称为结节性硬化复合物（TSC））的原因。另一个遗传疾病淋巴管平滑肌肌瘤病（LAM）也与TSC2基因的突变有关。 Hamartin和tuberin通过负调节S6激酶1（S6K1）和真核起始因子4E结合蛋白1（4E-BP1）来控制细胞生长，可能通过其上游的雷帕霉素哺乳动物靶标（mTOR）。生长因子和胰岛素促进了Akt / PKB依赖性的结核菌素磷酸化，进而使结核菌素的负调节作用释放了S6K1，并激活了S6K1。尽管关于TSC和LAM的分子遗传学方面已写了很多文章，这与TSC1和TSC2基因的丢失或突变有关，但很少有评论谈到由ha豆素和结核菌素调节的细胞内信号通路。当前的综述将填补我们对它们在细胞信号网络中作用的理解的空白，并且通过提高这种理解，关于结核菌素和ha玛汀的正常功能的综合图景开始出现。 （C）2003 Elsevier Science Inc.保留所有权利。 [参考：127]

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