Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling

被引：539

作者：

Gao, XS

Zhang, Y

Arrazola, P

Hino, O

Kobayashi, T

Yeung, RS

Ru, BG

Pan, DJ

机构：

[1] Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA

[2] Inst Canc Res, Dept Expt Pathol, Toshima Ku, Tokyo 1708455, Japan

[3] Univ Washington, Dept Surg, Div Med Genet, Seattle, WA 98195 USA

[4] Peking Univ, Dept Biochem, Beijing 100871, Peoples R China

来源：

NATURE CELL BIOLOGY | 2002年 / 4卷 / 09期

关键词：

D O I：

10.1038/ncb847

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Target of Rapamycin (TOR) mediates a signalling pathway that couples amino acid availability to S6 kinase (S6K) activation, translational initiation and cell growth(1,2). Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome(3,4), antagonize this amino acid-TOR signalling pathway. We show that Tsc1 and Tsc2 can physically associate with TOR and function upstream of TOR genetically. In Drosophila melanogaster and mammalian cells, loss of Tsc1 and Tsc2 results in a TOR-dependent increase of S6K activity. Furthermore, although S6K is normally inactivated in animal cells in response to amino acid starvation, loss of Tsc1-Tsc2 renders cells resistant to amino acid starvation. We propose that the Tsc1-Tsc2 complex antagonizes the TOR-mediated response to amino acid availability. Our studies identify Tsc1 and Tsc2 as regulators of the amino acid-TOR pathway and provide a new paradigm for how proteins involved in nutrient sensing function as tumour suppressors.

引用

页码：699 / 704

页数：6