Borrowing Transcriptional Kinases to Activate Apoptosis [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1029048 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26411900_1.fastq.gz | Fastqsanger.gz | |||
| SRR26411900_2.fastq.gz | Fastqsanger.gz | |||
| SRR26411901_1.fastq.gz | Fastqsanger.gz | |||
| SRR26411901_2.fastq.gz | Fastqsanger.gz | |||
| SRR26411902_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 46 |
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Project description:Kinases are critical regulators of cellular function that are commonly implicated in the mechanisms underlying disease. Most drugs that target kinases are molecules that inhibit their catalytic activity, but here we used chemically induced proximity to convert kinase inhibitors into activators of therapeutic genes. We synthesized bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs). These molecules relocalized CDK9 to BCL6-bound DNA and directed phosphorylation of RNA polymerase II. The resulting expression of pro-apoptotic, BCL6-target genes caused killing of diffuse large B cell lymphoma cells and specific ablation of the BCL6-regulated germinal center response. Genomics and proteomics corroborated a gain-of-function mechanism in which global kinase activity was not inhibited but rather redirected. Thus, kinase inhibitors can be used to context-specifically activate transcription. This PRIDE entry contains the raw proteomics data and DIA-NN search output.
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