p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling

Budanov AV, Karin M · 2008 · Cell · Atlas ID BUD2008

What this study shows

Connected DNA damage to mTOR. Two p53 target genes, Sestrin1 and Sestrin2, bound and activated AMPK and steered it to phosphorylate TSC2, which raised TSC2 GAP activity and lowered mTOR signalling. Sesn2-deficient mice failed to inhibit mTOR signalling after genotoxic challenge. This describes the stress-induced arm of Sestrin biology; the later leucine-sensing role of Sestrin2 through GATOR2 is a separate mechanism. Boundary: cell lines and mice under acute genotoxic stress; no human data.

Abstract

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The tumor suppressor p53 is activated upon genotoxic and oxidative stress and in turn inhibits cell proliferation and growth through induction of specific target genes. Cell growth is positively regulated by mTOR, whose activity is inhibited by the TSC1:TSC2 complex. Although genotoxic stress has been suggested to inhibit mTOR via p53-mediated activation of mTOR inhibitors, the precise mechanism of this link was unknown.

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 and mouse cell lines; Sesn2-deficient mice challenged with DNA damage) 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	Human and mouse cell lines; Sesn2-deficient mice challenged with DNA damage
Journal	Cell
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.cell.2008.06.028 · PMID 18692468 · Free full text (PMC2758522)

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	Sestrin1/2 overexpression and knockdown; genotoxic stress; Sesn2 knockout mice
Target	p53 -> Sestrin1/2 -> AMPK -> TSC2 -> mTOR
Model	Human and mouse cells; mice
Effect	Sestrins activate AMPK toward TSC2 and inhibit mTOR after DNA damage

In the Atlas

Links in the pathway map

Supports AMPK activates TSC1/TSC2

Cite this paper

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Budanov, A. V., & Karin, M. (2008). p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell. https://doi.org/10.1016/j.cell.2008.06.028

@article{BUD2008,
  author       = {Budanov, A. V. and Karin, M.},
  title        = {{p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling}},
  journal      = {Cell},
  year         = {2008},
  doi          = {10.1016/j.cell.2008.06.028},
  note         = {PMID: 18692468},
}

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 BUD2008) [Data set]. https://mtor-atlas.org/study/BUD2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_BUD2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record BUD2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/BUD2008/},
  doi          = {10.5281/zenodo.22059963}
}

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