TY - JOUR
T1 - Cell cycle–independent integration of stress signals by Xbp1 promotes Non-G1/G0 quiescence entry
AU - Argüello-Miranda, Orlando
AU - Marchand, Ashley J.
AU - Kennedy, Taylor
AU - Russo, Marielle A.X.
AU - Noh, Jungsik
N1 - Publisher Copyright:
© 2021 Argüello-Miranda et al.
PY - 2021/1/3
Y1 - 2021/1/3
N2 - 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.
AB - 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.
KW - Cell cycle and division
KW - Cell signaling
KW - Development
KW - Systems and Computational Biology
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U2 - 10.1083/jcb.202103171
DO - 10.1083/jcb.202103171
M3 - Article
C2 - 34694336
AN - SCOPUS:85120924293
SN - 0021-9525
VL - 221
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 1
M1 - e202103171
ER -