Cip1 tunes cell cycle arrest duration upon calcineurin activation

• Published in: Proceedings of the National Academy of Sciences - PNAS 2022-06, Vol.119 (23), p.1-10
• Main Authors: Flynn, Mackenzie J., Benanti, Jennifer A.
• Format: Article
• Language: English
• Subjects: Biological Sciences; Calcineurin; Calcineurin - metabolism; Cell activation; Cell cycle; Cell Cycle - physiology; Cell Cycle Checkpoints; Cell Cycle Proteins - metabolism; Cellular stress response; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Environmental stress; Enzyme inhibitors; Gene regulation; Hog1 protein; Kinases; Phosphorylation; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2202469119

Cells exposed to environmental stress arrest the cell cycle until they have adapted to their new environment. Cells adjust the length of the arrest for each unique stressor, but how they do this is not known. Here, we investigate the role of the stress-activated phosphatase calcineurin (CN) in controlling cell cycle arrest in Saccharomyces cerevisiae. We find that CN controls arrest duration through activation of the G1 cyclin–dependent kinase inhibitor Cip1. Our results demonstrate that multiple stressors trigger a G1/S arrest through Hog1-dependent down-regulation of G1 cyclin transcription. When a stressor also activates CN, this arrest is lengthened as CN prolongs Hog1-dependent phosphorylation of Cip1. Cip1 plays no role in response to stressors that activate Hog1 but not CN. These findings illustrate how stress response pathways cooperate to tailor the stress response and suggest that Cip1 functions to prolong cell cycle arrest when a cell requires additional time for adaptation.