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TY - JOUR AU - Gao, Xinsheng AU - Zhang, Yong AU - Arrazola, Peter AU - Hino, Okio AU - Kobayashi, Toshiyuki AU - Yeung, Raymond S. AU - Ru, Binggeng AU - Pan, Duojia PY - 2002 DA - 2002/09/01 TI - Tsc tumour suppressor proteins antagonize amino-acid–TOR signalling JO - Nature Cell Biology SP - 699 EP - 704 VL - 4 IS - 9 AB - Target of Rapamycin (TOR) mediates a signalling pathway that couples amino acid availability to S6 kinase (S6K) activation, translational initiation and cell growth1,2. Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome3,4, 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. SN - 1476-4679 UR - https://doi.org/10.1038/ncb847 DO - 10.1038/ncb847 ID - Gao2002 ER -