A Complex of the Srb8, -9, -10, and -11 Transcriptional Regulatory Proteins from Yeast

Borggrefe, Tilman; Davis, Roger T.; Erdjument‐Bromage, Hediye; Tempst, Paul; Kornberg, Roger D.

doi:10.1074/jbc.m207195200

Cited by 143 publications

(130 citation statements)

References 42 publications

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“…Another larger form, which contains four additional Mediator subunits, spSrb8, spTrap240, spSrb10, spSrb11, is always isolated devoid of pol II. These proteins collectively form the Srb8 -11 module, which was recently isolated in free form (31). We here demonstrate that Mediator isolated from a sptrap240 Ϫ deletion strain also lacks spSrb10.…”

Section: Discussionmentioning

confidence: 81%

Mediator Influences Schizosaccharomyces pombe RNA Polymerase II-dependent Transcription in Vitro

Spåhr

Khorosjutina

Baraznenok

et al. 2003

Journal of Biological Chemistry

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The fission yeast Schizosaccharomyces pombe has proved an important model system for cross-species comparative studies of many fundamental processes in the eukaryotic cell, such as cell cycle control and DNA replication. The RNA polymerase II transcription machinery is, however, still relatively poorly understood in S. pombe, partially due to the absence of a reconstituted in vitro transcription system. We have now purified S. pombe RNA polymerase II and its general initiation factors TFIIB, TFIIF, TFIIE, and TFIIH to near homogeneity. These factors enable RNA polymerase II to initiate transcription from the S. pombe alcohol dehydrogenase promoter (adh1p) when combined with Saccharomyces cerevisiae TATA-binding protein. We use our reconstituted system to examine effects of Mediator on basal transcription in vitro. S. pombe Mediator exists in two distinct forms, a free form, which contains the spSrb8, spTrap240, spSrb10, and spSrb11 subunits, and a smaller form, which lacks these four subunits and associates with RNA polymerase II to form a holoenzyme. We find that spSrb8/spTrap240/spSrb10/spSrb11 containing Mediator repress basal transcription, whereas Mediator lacking these subunits has a stimulatory effect on transcription. Our findings thus demonstrate that the spSrb8/spTrap240/spSrb10/spSrb11 subcomplex governs the ability of Mediator to stimulate or repress basal transcription in vitro.

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Section: Discussionmentioning

confidence: 81%

Mediator Influences Schizosaccharomyces pombe RNA Polymerase II-dependent Transcription in Vitro

Spåhr

Khorosjutina

Baraznenok

et al. 2003

Journal of Biological Chemistry

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“…About onequarter of the MED23 in a HeLa cell nuclear extract behaves as monomer, the remaining three-quarters being associated with Mediator complexes. No other Mediator subunit has been observed in a form separate from the complete Mediator complex, with the exception of the CDK8-CyclinC-MED12-MED13 complex (Borggrefe et al, 2002). This fortuitous occurrence of free MED23 simplified its identification as the Mediator subunit with which E1A CR3 interacts.…”

Section: E1a Conserved Region 3 Activation Of Early Viral Gene Expresmentioning

confidence: 99%

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

2005

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Adenovirus continues to be an important model system for investigating basic aspects of cell biology. Interactions of several cellular proteins with E1A conserved regions (CR) 1 and 2, and inhibition of apoptosis by E1B proteins are required for oncogenic transformation. CR2 binds RB family members, de-repressing E2F transcription factors, thus activating genes required for cell cycling. E1B-19K is a BCL2 homolog that binds and inactivates proapoptotic BAK and BAX. E1B-55K binds p53, inhibiting its transcriptional activation function. In productively infected cells, E1B-55K and E4orf6 assemble a ubiquitin ligase with cellular proteins Elongins B and C, Cullin 5 and RBX1 that polyubiquitinates p53 and one or more subunits of the MRN complex involved in DNA doublestrand break repair, directing them to proteosomal degradation. E1A CR3 activates viral transcription by interacting with the MED23 Mediator subunit, stimulating preinitiation complex assembly on early viral promoters and probably also the rate at which they initiate transcription. The viral E1B-55K/E4orf6 ubiquitin ligase is also required for efficient viral late protein synthesis in many cell types, but the mechanism is not understood. E1A CR1 binds several chromatin-modifying complexes, but how this contributes to stimulation of cellular DNA synthesis and transformation is not clear. E1A CR4 binds the CtBP corepressor, but the mechanism by which this modulates the frequency of transformation remains to be determined. Clearly, adenovirus has much left to teach us about fundamental cellular processes.

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“…This module is present in a subpopulation of the Mediator, is conserved among eukaryotes, and phosphorylates the Pol II CTD. [8][9][10][11] The CDK8/cyclin C module is a target of the Ras/PKA signal transduction pathway, 12 and is also involved in Notch signalling. 13 The CDK8/cyclin C pair has a role in transcriptional repression.…”

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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A Complex of the Srb8, -9, -10, and -11 Transcriptional Regulatory Proteins from Yeast

Cited by 143 publications

References 42 publications

Mediator Influences Schizosaccharomyces pombe RNA Polymerase II-dependent Transcription in Vitro

Mediator Influences Schizosaccharomyces pombe RNA Polymerase II-dependent Transcription in Vitro

Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus

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

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