The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network

Autoři: Cassandra M. Leech aff001;  Mackenzie J. Flynn aff001;  Heather E. Arsenault aff001;  Jianhong Ou aff001;  Haibo Liu aff001;  Lihua Julie Zhu aff001;  Jennifer A. Benanti aff001
Působiště autorů: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America aff001;  Program in Bioinformatics and Integrative Biology, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America aff002
Vyšlo v časopise: The coordinate actions of calcineurin and Hog1 mediate the stress response through multiple nodes of the cell cycle network. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008600
Kategorie: Research Article


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 stress signals and coordinate the appropriate adaptive response with cell cycle arrest. Here we investigate the role of the phosphatase calcineurin (CN) in the stress response and demonstrate that CN activates the Hog1/p38 pathway in both yeast and human cells. In yeast, the MAPK Hog1 is transiently activated in response to several well-studied osmostressors. We show that when a stressor simultaneously activates CN and Hog1, CN disrupts Hog1-stimulated negative feedback to prolong Hog1 activation and the period of cell cycle arrest. Regulation of Hog1 by CN also contributes to inactivation of multiple cell cycle-regulatory transcription factors (TFs) and the decreased expression of cell cycle-regulated genes. CN-dependent downregulation of G1/S genes is dependent upon Hog1 activation, whereas 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 to inhibit multiple nodes of the cell cycle-regulatory network. Our results suggest that crosstalk between CN and stress-activated MAPKs helps cells tailor their adaptive responses to specific stressors.

Klíčová slova:

Cell cycle and cell division – Cell cycle inhibitors – Cellular stress responses – Gene expression – Gene regulation – Phosphorylation – Synthesis phase – Cellular crosstalk


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