RT Journal Article
SR Electronic
T1 The coordinate actions of calcineurin and Hog1 mediate the response to cellular stress through multiple nodes of the cell cycle network
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 612416
DO 10.1101/612416
A1 Cassandra M. Leech
A1 Mackenzie J. Flynn
A1 Heather E. Arsenault
A1 Jianhong Ou
A1 Haibo Liu
A1 Lihua Julie Zhu
A1 Jennifer A. Benanti
YR 2019
UL http://biorxiv.org/content/early/2019/04/17/612416.abstract
AB Upon exposure to environmental stressors, cells transiently arrest the cell cycle while they adapt and restore homeostasis. A challenge for all cells is to distinguish between diverse stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the stress-activated phosphatase calcineurin (CN) in this process and show that CN utilizes multiple pathways to control the cell cycle. Upon activation, CN inhibits transcription factors (TFs) that regulate the G1/S transition through activation of the stress-activated MAPK Hog1. In contrast, CN inactivates G2/M TFs through a combination of Hog1-dependent and -independent mechanisms. These findings demonstrate that CN and Hog1 act in a coordinated manner at multiple nodes of the cell cycle-regulatory network to rewire gene expression and arrest cells in response to stress. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors.