Abstract
The budding yeast Saccharomyces cerevisiae differentiates into filamentous invasively growing forms under conditions of nutrient limitation1,2. This response is dependent on the transcription factor Ste12 and on the mating pheromone-response mitogen-activated protein (MAP) kinase cascade1, but a mechanism for regulation of Ste12 by nutrient limitation has not been defined. Here we show that Ste12 function in filamentous growth is regulated by the cyclin-dependent kinase Srb10 (also known as Cdk8), which is associated with the RNA polymerase II holoenzyme. Srb10 inhibits filamentous growth in cells growing in rich medium by phosphorylating Ste12 and decreasing its stability. Under conditions of limiting nitrogen, loss of Srb10 protein and kinase activity occurs, with a corresponding loss of Ste12 phosphorylation. Mutation of the Srb10-dependent phosphorylation sites increases pseudohyphal development but has no effect on the pheromone response of haploid yeast. Srb10 kinase activity is also regulated independently of the mating pheromone-response pathway. This indicates that Srb10 controls Ste12 activity for filamentous growth in response to nitrogen limitation and is consistent with the hypothesis that Srb10 regulates gene-specific activators in response to physiological signals to coordinate gene expression with growth potential.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Roberts, R. L. & Fink, G. R. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth. Genes Dev. 8, 2974–2985 (1994)
Cullen, P. J. & Sprague, G. F. Jr Glucose depletion causes haploid invasive growth in yeast. Proc. Natl Acad. Sci. USA 97, 13619–13624 (2000)
Madhani, H. D. & Fink, G. R. Combinatorial control required for the specificity of yeast MAPK signaling. Science 275, 1314–1317 (1997)
Morillon, A., Springer, M. & Lesage, P. Activation of the Kss1 invasive-filamentous growth pathway induces Ty1 transcription and retrotransposition in Saccharomyces cerevisiae. Mol. Cell. Biol. 20, 5766–5776 (2000)
Holstege, F. C. et al. Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95, 717–728 (1998)
Hung, W., Olson, K. A., Breitkreutz, A. & Sadowski, I. Characterization of the basal and pheromone-stimulated phosphorylation states of Ste12p. Eur. J. Biochem. 245, 241–251 (1997)
Boyle, W. J., van der Geer, P. & Hunter, T. Phosphopeptide mapping and phosphoamino acid analysis by two-dimensional separation on thin-layer cellulose plates. Methods Enzymol. 201, 110–149 (1991)
Pi, H., Chien, C. T. & Fields, S. Transcriptional activation upon pheromone stimulation mediated by a small domain of Saccharomyces cerevisiae Ste12p. Mol. Cell. Biol. 17, 6410–6418 (1997)
Olson, K. A. et al. Two regulators of Ste12p inhibit pheromone-responsive transcription by separate mechanisms. Mol. Cell. Biol. 20, 4199–4209 (2000)
Fields, S. & Herskowitz, I. Regulation by the yeast mating-type locus of STE12, a gene required for cell-type-specific expression. Mol. Cell. Biol. 7, 3818–3821 (1987)
Chang, Y. W., Howard, S. C., Budovskaya, Y. V., Rine, J. & Herman, P. K. The rye mutants identify a role for Ssn/Srb proteins of the RNA polymerase II holoenzyme during stationary phase entry in Saccharomyces cerevisiae. Genetics 157, 17–26 (2001)
Chi, Y. et al. Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev. 15, 1078–1092 (2001)
Rohde, J. R., Trinh, J. & Sadowski, I. Multiple signals regulate GAL transcription in yeast. Mol. Cell. Biol. 20, 3880–3886 (2000)
Gimeno, C. J., Ljungdahl, P. O., Styles, C. A. & Fink, G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell 68, 1077–1090 (1992)
Hirst, M., Kobor, M. S., Kuriakose, N., Greenblatt, J. & Sadowski, I. GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. Mol. Cell 3, 673–678 (1999)
Acknowledgements
We thank G. Sprague for plasmids; S. Hahn for antibodies against Srb10; and G. Mackie for comments. This research was supported by grants from the Canadian Institutes of Health Research (CIHR) and the National Cancer Institute of Canada (NCIC), with funds from the Canadian Cancer Society. C.N. was supported by a CIHR doctoral training award.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare that they have no competing financial interests.
Rights and permissions
About this article
Cite this article
Nelson, C., Goto, S., Lund, K. et al. Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nature 421, 187–190 (2003). https://doi.org/10.1038/nature01243
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/nature01243
This article is cited by
-
Transcriptional regulatory proteins in central carbon metabolism of Pichia pastoris and Saccharomyces cerevisiae
Applied Microbiology and Biotechnology (2020)
-
Suppression of wheat TaCDK8/TaWIN1 interaction negatively affects germination of Blumeria graminis f.sp. tritici by interfering with very-long-chain aldehyde biosynthesis
Plant Molecular Biology (2018)
-
A meta-analysis reveals complex regulatory properties at Taf14-repressed genes
BMC Genomics (2017)
-
FgSsn3 kinase, a component of the mediator complex, is important for sexual reproduction and pathogenesis in Fusarium graminearum
Scientific Reports (2016)
-
MicroRNA-101 is a potential prognostic indicator of laryngeal squamous cell carcinoma and modulates CDK8
Journal of Translational Medicine (2015)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.