A PERK–miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival

Dec 13, 2017Nature cell biology

A PERK and miR-211 pathway reduces daily rhythm regulators and protein production to help cancer cells survive

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Abstract

UPR activation induces a 10 h phase shift in circadian oscillations through the induction of miR-211.

  • The unfolded protein response (UPR) influences the circadian clock by affecting core regulators Bmal1 and Clock.
  • miR-211, which is induced by UPR activation, suppresses both Bmal1 and Clock through different mechanisms.
  • Suppression of Bmal1 and Clock alters the expression of certain circadian genes.
  • Repression of Bmal1 is crucial for UPR-mediated inhibition of protein synthesis and helps cells adapt to endoplasmic reticulum stress.
  • In Burkitt's lymphoma, c-Myc-dependent UPR activation suppresses Bmal1, which may contribute to tumour progression.

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