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Signalling

Stress and disease connect at mTORC1

Nature Reviews Cancer volume 8, page 325 (2008)Cite this article

...demonstrate that the ER is wired to the mTOR pathway to control nutrient homeostasis, insulin action and survival.

Previous work from the Hotamisligil laboratory showed that obesity causes ER stress and promotes the development of insulin resistance, which prompted the authors to investigate whether the block in insulin signalling that is associated with the loss of TSC genes might also be the result of ER stress. Indeed, both Tsc1 −/− and Tsc2 −/− mouse embryonic fibroblasts (MEFs) showed augmentation of markers of ER stress, including increased PERK phosphorylation, increased expression of genes involved in the unfolded protein response (UPR) and activation of JNK, an important negative regulator of insulin receptor (IR) signalling. Restoration of TSC function in the TSC-knockout MEFs reversed this effect. These findings were confirmed in vivo with a TSC-mutant mouse model and samples from TSC patients.

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References

ORIGINAL RESEARCH PAPER

  1. Ozcan, U. et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol. Cell 29, 541–551 (2008)

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FURTHER READING

  1. Reiling, J. H. & Sabatini, D. M. Increased mTORC1 signaling UPRegulates stress. Mol. Cell 29, 533–535 (2008)

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Authors and Affiliations

  1. Senior Editor, Nature Reviews Molecular Cell Biology,

    Ekat Kritikou

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  1. Ekat Kritikou
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Kritikou, E. Stress and disease connect at mTORC1. Nat Rev Cancer 8, 325 (2008). https://doi.org/10.1038/nrc2381

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  • DOI: https://doi.org/10.1038/nrc2381

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