Cell cycle–independent integration of stress signals by Xbp1 promotes Non-G1/G0 quiescence entry

Orlando Argüello-Miranda, Ashley J. Marchand, Taylor Kennedy, Marielle A.X. Russo, Jungsik Noh

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cellular quiescence is a nonproliferative state required for cell survival under stress and during development. In most quiescent cells, proliferation is stopped in a reversible state of low Cdk1 kinase activity; in many organisms, however, quiescent states with high-Cdk1 activity can also be established through still uncharacterized stress or developmental mechanisms. Here, we used a microfluidics approach coupled to phenotypic classification by machine learning to identify stress pathways associated with starvation-triggered high-Cdk1 quiescent states in Saccharomyces cerevisiae. We found that low-and high-Cdk1 quiescent states shared a core of stress-associated processes, such as autophagy, protein aggregation, and mitochondrial up-regulation, but differed in the nuclear accumulation of the stress transcription factors Xbp1, Gln3, and Sfp1. The decision between low-or high-Cdk1 quiescence was controlled by cell cycle–independent accumulation of Xbp1, which acted as a time-delayed integrator of the duration of stress stimuli. Our results show how cell cycle–independent stress-activated factors promote cellular quiescence outside G1/G0.

Original languageEnglish (US)
Article numbere202103171
JournalJournal of Cell Biology
Volume221
Issue number1
DOIs
StatePublished - Jan 3 2021

Keywords

  • Cell cycle and division
  • Cell signaling
  • Development
  • Systems and Computational Biology

ASJC Scopus subject areas

  • Cell Biology

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