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Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor III

ABSTRACT: Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor III

PROVIDER: PRJNA516418 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8471490.fastq.gz	Fastqsanger.gz
	SRR8471500.fastq.gz	Fastqsanger.gz
	SRR8471510.fastq.gz	Fastqsanger.gz
	SRR8471520.fastq.gz	Fastqsanger.gz
	SRR8471530.fastq.gz	Fastqsanger.gz

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Similar Datasets

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor III

Project description:The transcription factor NFAT has a key role in both T cell activation and tolerance and has emerged as an important target of immune modulation. NFAT directs the effector arm of the immune response in the presence of AP-1, and T cell anergy/exhaustion in the absence of AP-1. Envisioning a strategy for selective modulation of the immune response, we designed a FRET-based high-throughput screen to identify compounds that disrupt the NFAT:AP-1:DNA complex. We screened ~202,000 small organic compounds and identified 337 candidate inhibitors. We focus here on one compound, N-(3-acetamidophenyl)-2-[5-(1H-benzimidazol-2-yl)pyridin-2-yl]sulfanylacetamide (Compound 10), which disrupts the NFAT:AP-1 interaction at the composite ARRE-2 site without affecting the binding of NFAT or AP-1 alone to DNA. Compound 10 binds to DNA in a sequence-selective manner and inhibits the transcription of the Il2 gene and several other CsA-sensitive cytokine genes important for the effector immune response. This study provides proof-of-concept that small molecules can inhibit the assembly of specific DNA-protein complexes, and opens a potential new approach to treat human diseases where known transcription factors are deregulated.

2019-01-23 | GSE125445 | GEO

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor II

2019-01-23 | GSE125444 | GEO

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor I

2019-01-23 | GSE125443 | GEO

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

| PRJNA516414 | ENA

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor II

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor II

| PRJNA516419 | ENA

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor I

Project description:Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor I

| PRJNA516417 | ENA

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor.

Project description:The transcription factor nuclear factor of activated T cells (NFAT) has a key role in both T cell activation and tolerance and has emerged as an important target of immune modulation. NFAT directs the effector arm of the immune response in the presence of activator protein-1 (AP-1), and T cell anergy/exhaustion in the absence of AP-1. Envisioning a strategy for selective modulation of the immune response, we designed a FRET-based high-throughput screen to identify compounds that disrupt the NFAT:AP-1:DNA complex. We screened ?202,000 small organic compounds and identified 337 candidate inhibitors. We focus here on one compound, N-(3-acetamidophenyl)-2-[5-(1H-benzimidazol-2-yl)pyridin-2-yl]sulfanylacetamide (Compound 10), which disrupts the NFAT:AP-1 interaction at the composite antigen-receptor response element-2 site without affecting the binding of NFAT or AP-1 alone to DNA. Compound 10 binds to DNA in a sequence-selective manner and inhibits the transcription of the Il2 gene and several other cyclosporin A-sensitive cytokine genes important for the effector immune response. This study provides proof-of-concept that small molecules can inhibit the assembly of specific DNA-protein complexes, and opens a potential new approach to treat human diseases where known transcription factors are deregulated.

| S-EPMC6525529 | biostudies-literature

Targeting the NFAT:AP-1 transcriptional complex on DNA with a small-molecule inhibitor

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-01-23 | GSE125446 | GEO

Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma

Project description:Diffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.

2019-11-23 | GSE140882 | GEO

Targeting genes of AP-2d in the mouse midbrain

Project description:Identification of AP-2d target genes in the midbrain of E15 mouse embryos RNA from a pool of 15 E15 mouse midbrains from control and AP-2d knockout embryos

2011-07-31 | E-GEOD-27296 | biostudies-arrayexpress

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