The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
CDK8 is a positive regulator of transcriptional elongation within the serum response network
Open accessAbstract
The Mediator complex allows communication between transcription factors and RNA polymerase II (RNAPII). Cyclin-dependent kinase 8 (CDK8), the kinase found in some variants of Mediator, has been characterized mostly as a transcriptional repressor. Recently, CDK8 was demonstrated to be a potent oncoprotein. Here we show, using a human tumor cell line, that CDK8 is a positive regulator of genes within the serum response network, including several members of the activator protein 1 and early growth response family of oncogenic transcription factors. Mechanistic studies show that CDK8 is not required for RNAPII recruitment or promoter escape. Instead, CDK8 depletion leads to the appearance of slower elongation complexes carrying hypophosphorylated RNAPII. CDK8-Mediator regulates precise steps in the assembly of the RNAPII elongation complex, including the recruitment of positive transcription elongation factor b and BRD4. Furthermore, CDK8-Mediator specifically interacts with positive transcription elongation factor b. Thus, we have uncovered a role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects.
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Cites
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Recruitment of P-TEFb for Stimulation of Transcriptional Elongation by the Bromodomain Protein Brd4
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Cited by
The Mediator complex: a central integrator of transcription
Allen, B. L., & Taatjes, D. J. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3951 · Cited by 922
Self-citationGene regulation in the immediate-early response process
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“A binding site for the phosphoserine binding protein 14-3-3 is created by MSK1/2 (Macdonald et al., 2005), and this protein connects components of the transcription activation machinery, such as the lysine acetyltransferase PCAF and the SWI/SNFATPase BRG1 (Drobic et al., 2010).”
BackgroundBorn to run: control of transcription elongation by RNA polymerase II
Chen, F. X., Smith, E. R., & Shilatifard, A. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0010-5 · Cited by 447
Inhibitors of cyclin-dependent kinases as cancer therapeutics.
Whittaker, S. R., Mallinger, A., Workman, P., & Clarke, P. A. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.008 · Cited by 384
The Mediator complex and transcription regulation
Poss, Z. C., Ebmeier, C. C., & Taatjes, D. J. (2013) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2013.840259 · Cited by 364
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Metadata
- Authors
- Donner, A. J., Ebmeier, C. C., Taatjes, D. J., & Espinosa, J. M.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2010-01-24
- Volume
- 17
- Issue
- 2
- Pages
- 194-201
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2107295567
- Cited by
- 371
- References
- 60
- FWCI
- 10.63
- Type
- journal article
- Language
- en
- Open access
- green
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- Donner, A. J., Ebmeier, C. C., Taatjes, D. J., & Espinosa, J. M. (2010). CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.1752
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