Oliver's mTOR Atlas Evidence Platform
Reading level
Mode

Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb

Tee AR, Cantley LC et al. · 2003 · Current Biology · Atlas ID TEE2003

What this study shows

TSC1-TSC2 acts as a GTPase-activating protein (GAP) for Rheb; when TSC is inactive, Rheb accumulates in its active GTP-bound form and directly activates mTORC1.

Abstract

ShowHide

Tuberous Sclerosis Complex (TSC) is a genetic disorder that occurs through the loss of heterozygosity of either TSC1 or TSC2, which encode Hamartin or Tuberin, respectively. Tuberin and Hamartin form a tumor suppressor heterodimer that inhibits the mammalian target of rapamycin (mTOR) nutrient signaling input, but how this occurs is unclear. We show that the small G protein Rheb (Ras homolog enriched in brain) is a molecular target of TSC1/TSC2 that regulates mTOR signaling.

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: Human cell lines) 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 type5 - Mechanistic / In Vitro
Model systemHuman cell lines
JournalCurrent Biology
Year2003
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1016/s0960-9822(03)00506-2 · PMID 12906785

Extracted findings

InterventionBiochemical/genetic (TSC1/TSC2)
TargetTSC1-TSC2 (Hamartin/Tuberin) / Rheb / mTOR
ModelHuman cell lines
EffectTuberin-Hamartin (TSC1-TSC2) control mTOR by acting as a GAP complex toward Rheb

In the Atlas

Related topics

TSC1/TSC2mTORC1Rheb

More studies on this topic

Learn the biology

Want to understand the biology behind this study? → The TSC Complex — Where the Inputs Meet

Cite this paper

ShowHide 
Tee, A. R., et al. (2003). Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Current Biology. https://doi.org/10.1016/s0960-9822(03)00506-2

@article{TEE2003,
  author       = {Tee, A. R. and Cantley, L. C. and others},
  title        = {{Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb}},
  journal      = {Current Biology},
  year         = {2003},
  doi          = {10.1016/s0960-9822(03)00506-2},
  note         = {PMID: 12906785},
}

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 TEE2003) [Data set]. https://mtor-atlas.org/study/TEE2003/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_TEE2003,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record TEE2003},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/TEE2003/},
  doi          = {10.5281/zenodo.22059963}
}