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

J Cell Biol. 2022 Jan 3;221(1):e202103171. doi: 10.1083/jcb.202103171. Epub 2021 Oct 25.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle*
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Microfluidics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction*
  • Stress, Physiological*
  • Transcription Factors / metabolism

Substances

  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • XBP1 protein, S cerevisiae