Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

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

PROVIDER: PRJNA516419 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR8471450.fastq.gz	Fastqsanger.gz
	SRR8471460.fastq.gz	Fastqsanger.gz
	SRR8471470.fastq.gz	Fastqsanger.gz
	SRR8471480.fastq.gz	Fastqsanger.gz
	SRR8471451.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 36

Similar Datasets

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

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 | 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 III

2019-01-23 | GSE125445 | 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 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 III

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

| PRJNA516418 | 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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data