Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling

Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung RS, Ru B, Pan D · 2002 · Nature Cell Biology · Atlas ID GAO2002

What this study shows

The authors asked how the Tsc1 and Tsc2 tumour suppressors relate to TOR, the nutrient-sensing kinase. They showed that Tsc1 and Tsc2 can physically associate with TOR and act upstream of TOR in fly genetic tests. In fly and mammalian cells lacking Tsc1 or Tsc2, S6K activity rose, and this increase depended on TOR. S6K normally switches off when cells are starved of amino acids, but cells without Tsc1-Tsc2 stayed resistant to that starvation. The authors proposed that the Tsc1-Tsc2 complex restrains the TOR response to amino acids. Boundary: Drosophila and cultured mammalian cells; S6K activity is used as the readout of TOR. Later work placed amino acid sensing mainly on the Rag GTPase arm rather than through TSC, so the amino acid part of the model is not the current consensus.

Abstract

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Target of Rapamycin (TOR) mediates a signalling pathway that couples amino acid availability to S6 kinase (S6K) activation, translational initiation and cell growth. Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome, 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.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Drosophila melanogaster genetics (Tsc1/Tsc2 mutants); Tsc-deficient mammalian cells) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Drosophila melanogaster genetics (Tsc1/Tsc2 mutants); Tsc-deficient mammalian cells
Journal	Nature Cell Biology
Year	2002
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ncb847 · PMID 12172555

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Loss of Tsc1/Tsc2 (genetic)
Target	TOR-dependent S6K activity; response to amino acid starvation
Model	Drosophila melanogaster; mammalian cells
Effect	Tsc1/Tsc2 loss increases TOR-dependent S6K activity and makes it resistant to amino acid withdrawal

In the Atlas

Links in the pathway map

Supports TSC1/TSC2 inhibits mTORC1

Cite this paper

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Gao, X., Zhang, Y., Arrazola, P., Hino, O., Kobayashi, T., Yeung, R. S., Ru, B., & Pan, D. (2002). Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nature Cell Biology. https://doi.org/10.1038/ncb847

@article{GAO2002,
  author       = {Gao, X. and Zhang, Y. and Arrazola, P. and Hino, O. and Kobayashi, T. and Yeung, R. S. and Ru, B. and Pan, D.},
  title        = {{Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling}},
  journal      = {Nature Cell Biology},
  year         = {2002},
  doi          = {10.1038/ncb847},
  note         = {PMID: 12172555},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GAO2002) [Data set]. https://mtor-atlas.org/study/GAO2002/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GAO2002,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GAO2002},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GAO2002/},
  doi          = {10.5281/zenodo.22059963}
}

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