Inoki Ken, Corradetti Michael N, Guan Kun-Liang
Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nat Genet. 2005 Jan;37(1):19-24. doi: 10.1038/ng1494.
The mammalian target of rapamycin (mTOR) has a central role in the regulation of cell growth. mTOR receives input from multiple signaling pathways, including growth factors and nutrients, to stimulate protein synthesis by phosphorylating key translation regulators such as ribosomal S6 kinase and eukaryote initiation factor 4E binding protein 1. High levels of dysregulated mTOR activity are associated with several hamartoma syndromes, including tuberous sclerosis complex, the PTEN-related hamartoma syndromes and Peutz-Jeghers syndrome. These disorders are all caused by mutations in tumor-suppressor genes that negatively regulate mTOR. Here we discuss the emerging evidence for a functional relationship between the mTOR signaling pathway and several genetic diseases, and we present evidence supporting a model in which dysregulation of mTOR may be a common molecular basis, not only for hamartoma syndromes, but also for other cellular hypertrophic disorders.
雷帕霉素靶蛋白（mTOR）在细胞生长调控中起核心作用。mTOR接收来自多种信号通路的输入，包括生长因子和营养物质，通过磷酸化关键的翻译调节因子（如核糖体S6激酶和真核生物起始因子4E结合蛋白1）来刺激蛋白质合成。mTOR活性的高度失调与多种错构瘤综合征相关，包括结节性硬化症复合体、与PTEN相关的错构瘤综合征和黑斑息肉综合征。这些疾病均由负向调节mTOR的肿瘤抑制基因突变引起。在此，我们讨论mTOR信号通路与几种遗传疾病之间功能关系的新证据，并提供证据支持一个模型，即mTOR失调可能是一个共同的分子基础，不仅是错构瘤综合征的基础，也是其他细胞肥大性疾病的基础。
