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Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12


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.

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Figure 1: Phosphorylation of Ste12 by Srb10 inhibits filamentous responsive transcription.
Figure 2: Phosphorylation of Ser 261 and Ser 451 of Ste12 inhibits filamentous growth but not pheromone response.
Figure 3: Stability of Ste12 is controlled by Srb10.
Figure 4: Nitrogen limitation inhibits Srb10 in vivo.

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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.

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Correspondence to Ivan Sadowski.

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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).

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