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Effects of CDK8/19 mediator kinase inhibition by didehydrocortistatin A (dCA) and 15w on gene expression in HEK293 cells

ABSTRACT: Effects of CDK8/19 mediator kinase inhibition by didehydrocortistatin A (dCA) and 15w on gene expression in HEK293 cells

PROVIDER: PRJNA826476 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18743966_1.fastq.gz	Fastqsanger.gz
	SRR18743966_2.fastq.gz	Fastqsanger.gz
	SRR18743967_1.fastq.gz	Fastqsanger.gz
	SRR18743967_2.fastq.gz	Fastqsanger.gz
	SRR18743968_1.fastq.gz	Fastqsanger.gz

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Effects of CDK8/19 mediator kinase inhibition by didehydrocortistatin A (dCA) and 15w on gene expression in HEK293 cells

Project description:RNA-Seq analysis was carried out to investigate the effects of selective CDK8/19 inhibitor didehydrocortistatin A (dCA) and 15w on gene expression in HEK293 cells (293-WT) or the CDK8/19 double-knockout (293-dKO) derivatives.

2023-06-30 | GSE200747 | GEO

The Cdk8 kinase module regulates Mediator-RNA polymerase II interaction

Project description:The Cdk8 kinase module (CKM) is a dissociable part of the coactivator complex Mediator that regulates RNA polymerase II (Pol II transcription. The CKM has negative and positive functions in gene transcription that remain poorly understood at the mechanistic level. Here, we prepare recombinant CKM from the yeast Saccharomyces cerevisiae and show that it binds core Mediator (cMed) to sterically inhibit cMed binding to the Pol II preinitiation complex (PIC) in vitro. We further show that the Cdk8 kinase activity of CKM counteracts CKM-cMed interaction,thereby releasing CKM and enabling Mediator to bind the PIC. Finally, we report that the kinase activity of Cdk8 is required for gene activation during heat shock in vivo, but not under steady state growth conditions. These results converge with previous literature on a model for CKM function. In this model, CKM negatively regulates Mediator function at upstream activating sequences by preventing Mediator binding to the PIC at the promoter. During gene activation, Cdk8 kinase activity may release Mediator and allow its binding to the PIC, thereby stimulating transcription initiation and accounting for the positive function of CKM.

2021-06-16 | GSE161140 | GEO

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

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.

2023-06-30 | GSE221160 | GEO

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

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

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Transcriptomic analysis of the effects of expression of CDK8/CDK19 and their kinase-inactive mutants in HEK293 cells (WT) and their CDK8/19 double-knockout (dKO) derivatives

Project description:RNA-Seq analysis was carried out to investigate the effects of expression of wild-type CDK8 (CDK8) or CDK19 (CDK19) or their kinase-inactive D173A mutants (CDK8M and CDK19M) in HEK293 cells (WT) and their CDK8/19 double-knockout (dKO) derivatives

2023-06-30 | GSE200753 | GEO

CDK8 Mediator kinase drives colon cancer hepatic metastasis by regulating gene expression of the matrix metalloproteinase network [Illumina]

Project description:CDK8 Mediator kinase is amplified and overexpressed in colon cancers; elevated CDK8 expression is associated with shorter patient survival. Nevertheless, CDK8 kinase inhibitors do not generally suppress colon cancer growth. We addressed this paradox by investigating the effects of CDK8 knockdown or a CDK8 kinase inhibitor on tumor growth at primary and metastatic sites. CDK8 knockdown or inhibition had no significant effect on primary tumors but suppressed the growth of hepatic metastases in murine and human colon cancer models. The effect of CDK8 inhibition on liver metastasis is mediated by upregulation of matrix metalloproteinase (MMP) inhibitor TIMP3 and downregulation of several MMPs.

2017-10-16 | GSE104963 | GEO

CDK8 Mediator kinase drives colon cancer hepatic metastasis by regulating gene expression of the matrix metalloproteinase network [Affymetrix]

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Effects of CDK8/19 Mediator Kinase inhibition by BI1347 and depletion by SNX7886 on gene expression in HEK293 cells

Project description:RNA-Seq analysis was carried out to investigate the effects of selective CDK8/19 inhibitor BI1347 and PROTAC degrader SNX7886 on gene expression in HEK293 cells (293-WT) or the CDK8/19 double-knockout (293-dKO) derivatives.

2023-08-21 | GSE231891 | GEO

Transcriptional responses to interferon require Mediator kinase-dependent pause release and mechanistically distinct functions of CDK8 and CDK19

Project description:Transcriptional responses to interferon require Mediator kinase-dependent pause release and mechanistically distinct functions of CDK8 and CDK19.

2019-07-15 | GSE129501 | GEO

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