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Systemic stress signalling: understanding the cell non-autonomous control of proteostasis

Abstract

Proteome maintenance is crucial to cellular health and viability, and is typically thought to be controlled in a cell-autonomous manner. However, recent evidence indicates that protein-folding defects can systemically activate proteostasis mechanisms through signalling pathways that coordinate stress responses among tissues. Coordination of ageing rates between tissues may also be mediated by systemic modulation of proteostasis. These findings suggest that proteome maintenance is a systemically regulated process, a discovery that may have important therapeutic implications.

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Figure 1: A model for the cell non-autonomous regulation of the cytosolic HSR in Caenorhabditis elegans.
Figure 2: Cell non-autonomous regulation of the UPRmt in Caenorhabditis elegans.
Figure 3: Cell non-autonomous regulation of the UPRER in Caenorhabditis elegans and mammalian cells.
Figure 4: Cell non-autonomous regulation of proteostasis by insulin-like signalling and gonadal signalling.

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Acknowledgements

The authors thank S. Wolff for her insightful ideas and comments. R.C.T. was funded by an Ellison Medical Foundation/American Federation for Aging Research (AFAR) Postdoctoral Fellowship. A.D. is cofounder of Proteostasis Therapeutics, Inc. and declares no financial interest related to this work. This work was supported by US NIH grant R01 AG042679.

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Taylor, R., Berendzen, K. & Dillin, A. Systemic stress signalling: understanding the cell non-autonomous control of proteostasis. Nat Rev Mol Cell Biol 15, 211–217 (2014). https://doi.org/10.1038/nrm3752

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