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

Nelson, Christopher E.; Goto, Susan; Lund, Karen; Hung, Wesley; Sadowski, Ivan

doi:10.1038/nature01243

Cited by 146 publications

(172 citation statements)

References 15 publications

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“…15 Further, CDK8 phosphorylates certain gene-specific transcription factors and decreases their stability. 16,17 However, there are some reports of a positive effect of CDK8/cylin C on transcription. CDK8-dependent phosphorylation of the gene-specific transcription factor Sip4 can stimulate transcription.…”

Section: Introductionmentioning

confidence: 99%

Structure of the Mediator Subunit Cyclin C and its Implications for CDK8 Function

Hoeppner¹,

Baumli²,

Cramer³

2005

Journal of Molecular Biology

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Cyclin C binds the cyclin-dependent kinases CDK8 and CDK3, which regulate mRNA transcription and the cell cycle, respectively. The crystal structure of cyclin C reveals two canonical five-helix repeats and a specific N-terminal helix. In contrast to other cyclins, the N-terminal helix is short, mobile, and in an exposed position that allows for interactions with proteins other than the CDKs. A model of the CDK8/cyclin C pair reveals two regions in the interface with apparently distinct roles. A conserved region explains promiscuous binding of cyclin C to CDK8 and CDK3, and a non-conserved region may be responsible for discrimination of CDK8 against other CDKs involved in transcription. A conserved and cyclin C-specific surface groove may recruit substrates near the CDK8 active site. Activation of CDKs generally involves phosphorylation of a loop at a threonine residue. In CDK8, this loop is longer and the threonine is absent, suggesting an alternative mechanism of activation that we discuss based on a CDK8-cyclin C model.

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Section: Introductionmentioning

confidence: 99%

Structure of the Mediator Subunit Cyclin C and its Implications for CDK8 Function

Hoeppner¹,

Baumli²,

Cramer³

2005

Journal of Molecular Biology

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“…Mediator containing the Srb8 to -11 subunits is always present in free form whereas Mediator lacking this submodule may associate with pol II. The relative levels of Srb8-11 vary because this submodule is degraded when yeast is grown under conditions of nutrient limitation (17,18), and the relative levels are also sensitive to the extraction procedure (19).…”

mentioning

confidence: 99%

Site-specific Srb10-dependent phosphorylation of the yeast Mediator subunit Med2 regulates gene expression from the 2-μm plasmid

Hallberg

Polozkov

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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The yeast Mediator complex is required for transcriptional regulation both in vivo and in vitro, and its function is conserved in all eukaryotes. Mediator interacts with both transcriptional activators and RNA polymerase II, but little is known about the mechanisms by which it operates at the molecular level. Here, we show that the cyclin-dependent kinase Srb10 interacts with, and phosphorylates, the Med2 subunit of Mediator both in vivo and in vitro. A point mutation of the single phosphorylation site in Med2 results in a strongly reduced expression of the REP1, REP2, FLP1, and RAF1 genes, which are all located on the endogenous 2-m plasmid. Combined with previous studies on the effects of SRB10͞SRB11 deletions, our data suggest that posttranslational modifications of Mediator subunits are important for regulation of gene expression.transcriptional regulation ͉ Srb11 ͉ RNA polymerase II T he Mediator complex was originally identified in Saccharomyces cerevisiae as an activity required for transcriptional activation in an in vitro transcription system reconstituted from highly purified RNA polymerase II (pol II) and general transcription factors (1, 2). Mediator was later purified to homogeneity and shown to be a complex composed of 20 subunits that interacts with the C-terminal domain of the largest pol II subunit (3, 4). More recent work has described several subunit-subunit interactions and subdomains within Mediator (5-8), and lowresolution structures of Mediator alone or in complex with pol II have been determined by three-dimensional reconstruction from electron micrographs of single particles (9, 10). These structures indicate a division of Mediator into distinct domains.In parallel with the identification of yeast Mediator, a pol II holoenzyme that comprised both Mediator subunits [a subset of general transcription factors and additional proteins (i.e., Srb8-11)] was purified (11). Nine SRB genes

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“…In addition to its positive role in gene activation (2,(5)(6)(7)20), Srb10͞11 has also been characterized as required for efficient repression by Tup1͞Ssn6, a protein complex that is recruited to and works at many yeast genes (12,(21)(22)(23)(24)(25). Suggestions as to the mechanism of this effect have been proposed, but the matter has not been fully resolved (1,3,8,21,22).…”

Section: Discussionmentioning

confidence: 99%

“…In the experiments shown here, each activating region, a deletion derivative of that used for Fig. 1, was attached to CTD 3 . The results show that, at subsaturating concentrations of substrate (see below), phosphorylation of the CTD 3 increased as the strength of the attached activating region increased (lanes 3-6).…”

Section: Methodsmentioning

confidence: 99%

“…The effect of the modification is unique to each case. For example, phosphorylation of Gal4 increases the efficiency of induction of the galactose-responsive genes; that of Gcn4 and Ste12 leads to their proteolysis; that of Msn2 leads to its export from the nucleus; and that of Sip4 increases the efficiency of induction of glucoseresponsive genes (1)(2)(3)(4)(5). Srb10͞11 also phosphorylates a heptapeptide (YSPTSPS), 26 tandem copies of which comprise the carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (6)(7)(8)(9).…”

mentioning

confidence: 99%

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Transcriptional activating regions target attached substrates to a cyclin-dependent kinase

Ansari

Ogirala²,

Ptashne³

2005

Proc. Natl. Acad. Sci. U.S.A.

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The yeast cyclin-dependent kinase Srb10 phosphorylates various transcriptional activators as they activate transcription, and acidic transcriptional activating domains found on several activators directly bind Srb10. Here we show that the interaction between Srb10 (with its associated cyclin Srb11) and each of several different activating regions, in vitro, leads to the phosphorylation of peptide sequences attached to but outside of the activating regions themselves. In some cases, residues within the activating regions are also phosphorylated. The results define a mechanism by which a kinase is recruited to alternate substrates with diverse physiological consequences.kinase-substrate targeting ͉ proteolysis ͉ Srb10͞11 ͉ transcriptional regulation

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

Cited by 146 publications

References 15 publications

Structure of the Mediator Subunit Cyclin C and its Implications for CDK8 Function

Structure of the Mediator Subunit Cyclin C and its Implications for CDK8 Function

Site-specific Srb10-dependent phosphorylation of the yeast Mediator subunit Med2 regulates gene expression from the 2-μm plasmid

Transcriptional activating regions target attached substrates to a cyclin-dependent kinase

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