Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex

Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG · 2004 · Genes & development · Atlas ID BRU2004

What this study shows

Hypoxia inhibits mTOR via REDD1-dependent activation of the TSC1/2 complex.

Abstract

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Mammalian target of rapamycin (mTOR) is a central regulator of protein synthesis whose activity is modulated by a variety of signals. Energy depletion and hypoxia result in mTOR inhibition. While energy depletion inhibits mTOR through a process involving the activation of AMP-activated protein kinase (AMPK) by LKB1 and subsequent phosphorylation of TSC2, the mechanism of mTOR inhibition by hypoxia is not known. Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: 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	Mammalian cells
Journal	Genes & development
Year	2004
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1101/gad.1256804 · PMID 15545625 · Free full text (PMC534650)

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	Genetic (REDD1 / TSC1-TSC2)
Target	mTOR / REDD1 / TSC1-TSC2
Model	Mammalian cells
Effect	Hypoxia inhibits mTOR via REDD1 acting through the TSC1/TSC2 tumor-suppressor complex

In the Atlas

Links in the pathway map

Supports Hypoxia activates REDD1 (DDIT4)
Supports REDD1 (DDIT4) activates TSC1/TSC2

Cite this paper

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Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004). Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes & development. https://doi.org/10.1101/gad.1256804

@article{BRU2004,
  author       = {Brugarolas, J. and Lei, K. and Hurley, R. L. and Manning, B. D. and Reiling, J. H. and Hafen, E. and Witters, L. A. and Ellisen, L. W. and Kaelin, W. G.},
  title        = {{Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex}},
  journal      = {Genes & development},
  year         = {2004},
  doi          = {10.1101/gad.1256804},
  note         = {PMID: 15545625},
}

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 BRU2004) [Data set]. https://mtor-atlas.org/study/BRU2004/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BRU2004,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BRU2004},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BRU2004/},
  doi          = {10.5281/zenodo.22059963}
}

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