Hog1 Targets Whi5 and Msa1 Transcription Factors To Downregulate Cyclin Expression upon Stress

Abstract

Yeast cells have developed complex mechanisms to cope with extracellular insults. An increase in external osmolarity leads to activation of the stress-activated protein kinase Hog1, which is the main regulator of adaptive responses, such as gene expression and cell cycle progression, that are essential for cellular survival. Upon osmostress, the G₁-to-S transition is regulated by Hog1 through stabilization of the cyclin-dependent kinase inhibitor Sic1 and the downregulation of G₁ cyclin expression by an unclear mechanism. Here, we show that Hog1 interacts with and phosphorylates components of the core cell cycle transcriptional machinery such as Whi5 and the coregulator Msa1. Phosphorylation of these two transcriptional regulators by Hog1 is essential for inhibition of G₁ cyclin expression, for control of cell morphogenesis, and for maximal cell survival upon stress. The control of both Whi5 and Msa1 by Hog1 also revealed the necessity for proper coordination of budding and DNA replication. Thus, Hog1 regulates G₁ cyclin transcription upon osmostress to ensure coherent passage through Start.

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01279-14.

ACKNOWLEDGMENTS

We thank Laia Subirana and Aida Fernandez for technical support and Alba Duch, Matteo Viganò, and Martí Aldea (IBMB) for cell cycle discussions.

We have no competing financial interests to declare.

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2012-33503 and FEDER to F.P. and BFU2011-26722 to E.D.N.) and 2014 SGR 599 (Generalitat de Catalunya). This project is supported by Fundación Botín and by Banco Santander through its Santander Universities Global Division to F.P. F.P. and E.D.N. are recipients of an ICREA Acadèmia award (Generalitat de Catalunya).