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Unfolded protein response

Pro-survival clock sUPRession

Nature Reviews Molecular Cell Biology volume 19, pages 74–75 (2018)Cite this article

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suppression of core circadian genes ... contributes to translation repression and cell survival following UPR activation

The authors observed that chemical induction of the UPR in mouse cultured cells and liver tissue caused an 8–10 h shift in circadian gene oscillation, which was abrogated by removal of PERK. Alterations in the normal light–dark cycle also triggered PERK activation in murine livers, revealing previously unanticipated layers of communication between the circadian clock and the UPR. Furthermore, induction of the UPR decreased Clock and Bmal1 protein levels in a PERK-dependent manner. Inhibition of miR-211 was sufficient to counteract the reduction in Clock and Bmal1 protein levels and the shift in the oscillations of the Clock and Bmal1 mRNAs after UPR induction in cultured cells. Thus, the UPR–PERK–miR-211 axis suppresses the expression of circadian clock genes.

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References

  1. Bu, Y. et al. A PERK–miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival. Nat. Cell Biol. http://dx.doi.org/10.1038/s41556-017-0006-y (2017)

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  1. Paulina Strzyz
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Strzyz, P. Pro-survival clock sUPRession. Nat Rev Mol Cell Biol 19, 74–75 (2018). https://doi.org/10.1038/nrm.2017.137

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