Hog1 targets Whi5 and Msa1 transcription factors to downregulate cyclin expression upon stress.
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.
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Alberto
A
González-Novo
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain Departament de Ciències Bàsiques, Facultat de Medicina i Ciències de la Salut, Universitat Internacional de Catalunya, Barcelona, Spain.
Javier
J
Jiménez
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain Departament de Ciències Bàsiques, Facultat de Medicina i Ciències de la Salut, Universitat Internacional de Catalunya, Barcelona, Spain.
Josep
J
Clotet
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Mariona
M
Nadal-Ribelles
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Santiago
S
Cavero
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain eulalia.nada@upf.edu francesc.posas@upf.edu.
Eulàlia
E
de Nadal
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain eulalia.nada@upf.edu francesc.posas@upf.edu.
Francesc
F
Posas
D018797:Cell Cycle Proteins / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics*; D015536:Down-Regulation; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009997:Osmotic Pressure; D060066:Protein Interaction Maps; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D016213:Cyclins; C529154:Msa1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C508130:Whi5 protein, S cerevisiae; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases