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Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin B in HCT116 and HEK293 cells treated with or without TNF-alpha

ABSTRACT: Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin B in HCT116 and HEK293 cells treated with or without TNF-alpha

PROVIDER: PRJNA395026 | ENA |

REPOSITORIES: ENA

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Effects of CDK8/19 Mediator Kinase inhibition by Senexin B on gene expression in HEK293 cells

Project description:RNA-Seq analysis was carried out to investigate the effects of selective CDK8/19 inhibitor Senexin B on gene expression in HEK293 cells (293-WT) or the CDK8/19 double-knockout (293-dKO) derivatives.

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Effects of CDK8/19 Mediator Kinase inhibition by Senexin B in HEK293 cells treated with or without Interferon-gamma

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Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin A in HEK293 cells treated with TNF-alpha II

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Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin A in HEK293 cells treated with TNF-alpha I

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Effects of Inhibition of CDK8/19 Mediator Kinase by Senexin B in HEK293 cells treated with or without TNF-alpha

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Project description:We have investigated the effects of CDK8/19 inhibitor Senexin B on NFκB-mediated transcription, induced by a canonical NFκB activator, TNFα.

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Project description:RNA-Seq analysis was carried out to investigate the effects of selective CDK8/19 inhibitor Senexin B (different treatment period) and knockout/re-expression of CDK8 and CDK19 proteins) on gene transcription in HEK293 cells

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Effects of Inhibition of CDK8/19 Mediator Kinase on serum-regulated gene expression in 293 cells

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24hr CA treatment vs. DMSO in HCT116 cells (from 'Identification of CDK8 and CDK19 substrates in human cells using cortistatin A and quantitative phosphoproteomics')

Project description:Cortistatin A (CA) is a highly selective inhibitor of the Mediator kinases CDK8 and CDK19. Using CA, we report here the first large-scale identification of Mediator kinase substrates in human cells (HCT116). Among over 16,000 quantified phosphosites, we identified 78 high-confidence Mediator kinase targets within 64 proteins, including DNA-binding transcription factors and proteins associated with chromatin, DNA repair, and RNA polymerase II. Although RNA-Seq data correlated with Mediator kinase targets, CA effects on gene expression were limited and distinct from CDK8 or CDK19 knockdown. Quantitative proteome analyses, which tracked about 7,000 proteins across six time points (0 â?? 24h), revealed that CA selectively affected pathways implicated in inflammation, growth, and metabolic regulation; contrary to expectations, increased turnover of Mediator kinase targets was not generally observed. Collectively, these data support Mediator kinases as regulators of chromatin and RNA polymerase II activity and suggest cellular roles beyond transcription, including metabolism and DNA repair. HCT116 cells were treated with either 100nM CA or DMSO in biological triplicate for each population (6 samples total). Treatment was for 24h for compound and vehicle.

2016-02-26 | E-GEOD-78506 | biostudies-arrayexpress

The Cdk8 kinase module regulates Mediator-RNA polymerase II interaction

Project description:We use biochemically reconstituted transcription initiation components including the Mediator core and Cdk8 kinase modules (CKM) to investigate the function of the CKM in regulating the Mediator-RNA polymerase II interaction in a highly purified system. We use cross-linking coupled to mass spectrometry to map the interaction of the CKM and core Mediator, and in vitro phosphorylation assays followed by phosphopeptide enrichment coupled to mass spectrometry to identify Cdk8 phosphorylation targets in this context and biochemically dissect their functions. Finally, we investigate the function of phosphorylation by Cdk8 on transcription in vivo. Based on that, we propose a model to integrate the phosphorylation-dependent and -independent functions of the CKM in transcription initiation.

2021-04-28 | PXD023361 | Pride

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