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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2010 August 27; 285(35): e99963.
PMCID: PMC2930749

Quantity Meets Quality at mTOR Junction♦

mTORC1 Links Protein Quality and Quantity Control by Sensing Chaperone Availability

♦ See referenced article, J. Biol. Chem. 2010, 285, 27385–27395

Proper cellular function requires maintaining the right balance of protein synthesis and degradation. To that end cells need to be able to sense numerous environmental cues such as nutrient availability, as well as internal status such as the extent of protein misfolding. Little is known about how cells integrate all these distinct pieces of information, but in this Paper of the Week, Shu-Bing Qian and colleagues demonstrate that chaperone availability acts a sensor of abnormal protein levels and that it signals through mTOR Complex 1 (mTORC1) to regulate protein synthesis. They employed various means of inducing cellular stress and showed that moderate accumulation of misfolded proteins, and thus a slight reduction of chaperone availability, enhanced mTORC1 signaling. In contrast, severe stress and a complete depletion of chaperoning capacity suppressed mTORC1 signaling. To substantiate these observations, Qian and colleagues used RNAi knockdown to directly reduce Hsp90 levels and found similar increases in mTORC1 activity. The mTOR pathway is already known to modulate cell responses to nutrient availability, and now these results show that mTOR integrates quantity and quality cues to maintain protein homeostasis.

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Heat shock treatment produces a rapid increase in phosphorylated S6 kinase 1 (a direct target of mTORC1) before even the heat shock-induced expression of Hsp70, suggesting that reduced chaperone availability increases mTORC1 signaling.

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Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology