Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gadd45a Knockout Alleviates Cisplatin-Induced Hearing Loss by Inhibiting CXCL Family Protein Expression

ABSTRACT: Gadd45a knockout inhibits cisplatin-induced cell death in the OC1 cell line. Transcriptome sequencing revealed that Gadd45a knockout suppresses the expression of CXCL family cytokines. This finding was further validated by protein-sequencing of the cell culture supernatant. Mechanistically, Gadd45a knockout specifically inhibits NF-κB1 (p105/p50) but not RELA (p65), both of which are transcription factors for CXCL family genes. Immunofluorescence staining demonstrated that Gadd45a knockout inhibits the nuclear translocation of NF-κB1 protein, but not that of RELA. In vivo, both si-Gadd45a injection into the semicircular canal and conditional knockout of Gadd45a effectively attenuated cisplatin-induced ototoxicity.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Zuhong He

PROVIDER: PXD072616 | iProX | Sat Jan 03 00:00:00 GMT 2026

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

RNA-sequencing in Mouse Embryonic Fibroblasts exposed to different Intensities of Hyperosmotic Stress

Project description:The inability of cells to adapt to increased environmental tonicity can lead to inflammatory gene expression and pathogenesis. The Rel family of transcription factors TonEBP and NF-κB p65 play critical roles in the switch from osmoadaptive homeostasis to inflammation, respectively. Here we identified a marker of the termination of adaptation and initiation of inflammation. We found that high stress inhibits protein interactions essential for the increased expression of TonEBP-dependent osmoprotective genes. This resulted in enhanced formation of TonEBP/NF-κB p65 complexes and enhanced proinflammatory gene expression.

2019-10-11 | GSE138692 | GEO

Cellular Mg2+ decrease causes a distinctive NF-κB-dependent form of cell death

Project description:Mg2+ is an essential cofactor for numerous enzymes, supporting fundamental cellular processes. Phosphatase of regenerating liver (PRL) protein family, inhibits cyclin M (CNNM) Mg2+ efflux transporters. To elucidate the physiological role of PRL in Mg2+ homeostasis at the cellular level, we employed combined genetic knockout and knockdown approaches. Such PRL KO + KD led to marked reduction of intracellular Mg2+ levels and triggered extensive cell death. To investigate the mechanism underlying cell death induced by PRL KO + KD, we next performed transcriptomic analysis to profile the changes in global gene expression, which revealed activation of the NF-κB pathway, and accordingly, genetic deletion of NF-κB p65 subunit abrogated cell death. Similarly, CNNM overexpression triggered intracellular Mg2+ decrease, NF-κB activation and subsequent cell death. Notably, this form of cell death exhibited unique morphological features, including actin-driven fiber-like protrusions, distinguishing it from known cell death modalities. Our findings uncover a previously unrecognized mode of NF-κB-dependent cell death triggered by intracellular Mg2+ decrease.

2026-01-03 | GSE309910 | GEO

Gene expression in LPS stimulated IkappaB-beta knockout bone marrow derived macrophage (BMDM)

Project description:Inflammation is beneficial when it is part of the innate immune response, but harmful when it occurs in an unregulated, chronic manner. We now report that IkappaB-beta, a member of the classical IkappaB family, serves a dual role of both inhibiting and facilitating the inflammatory response. IkappaB-beta degradation releases NF-kappaB dimers which upregulate proinflammatory target genes such as TNF-alpha. Suprisingly absence of IkappaB-beta results in a dramatic reduction of TNF-alpha in response to LPS even though the activation of NF-kappaB is normal. The inhibition of TNF-alpha mRNA expression can be correlated to the absence of nuclear, hypophosphorylated-IkappaB-beta bound to p65:cRel heterodimers at a specific kappaB site on the TNF-alpha promoter. Therefore IkappaB-beta acts through p65:cRel dimers to maintain prolonged expression of TNF-alpha. As a result, IkappaB-beta knockout mice are resistant to LPS induced septic shock and collagen-induced arthritis, and therefore blocking IkappaB-beta might be a promising new strategy for selectively inhibiting the chronic phase of TNF-alpha producting during the inflammatory response. Wild type and IkappaB-beta knockout BMDM cells were stimulated with LPS(1ug/ml) for 0, 1, and 5 hours. RNA isolated from the cells was analyzed on Affymetrix Mouse Genome 430A 2.0 gene expression chip.

2010-06-16 | E-GEOD-22223 | biostudies-arrayexpress

MiR-520b inhibits endothelial activation by targeting NF-κB p65

Project description:MiR-520b inhibits endothelial activation by targeting NF-κB p65

| PRJNA655883 | ENA

Timecourse of gene expression in HeLa cells (parental cells and clonal knockouts of MED12 and MED24) following induction by TNFa or IL-1b

Project description:Activation of nuclear factor kappa B (NF-kB) by inflammatory signals results in nuclear translocation of the transcription factor p65 and induction of gene expression. We identified MED12 and MED24 in an optical pooled CRISPR knockout screen in HeLa-Cas9 cells for genes affecting the activation and/or relaxation of p65 to the cytoplasm following induction by either TNFa or IL-1b. We generated isogenic clonal knockout HeLa-Cas9 lines using crRNA transfection and confirmed that loss of MED12 or MED24 results in delayed relaxation of p65, assayed by live-cell imaging of a p65-mNeonGreen fluorescent fusion.

2019-10-01 | GSE132704 | GEO

p65-HaloTag copurifying proteins in human 293T cells

Project description:In effort to develop methodology for targeted top down mass spectrometry of NF kappa B p65 from human cells, we evaluated the utility of HaloTag for purification and analysis of recombinant protein. During our study, two datasets of bottom up LC-MS/MS were generated: one from in-gel digestion of the predominant band following p65-HaloTag purification, another from in-solution digestion of all the proteins present in a p65-HaloTag purification. p65-HaloTag copurifying proteins identified in our datasets include the known interactors c-Rel, NF-kappaB p105, NF-kappaB p100, and NF-kappaB inhibitor beta. Over 100 proteins were identified by at least two peptides using a Mascot ion cut-off score of 30.

2018-10-19 | PXD001932 | Pride

Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function.

Project description:Deletion of the NF-κB subunit p65/RelA in the hematopoietic compartment results in gene expression changes in lineage-Flk2-c-kit+Sca-1+ cells from mouse bone marrow. We analyzed lineage-Flk2-c-kit+Sca-1+ cells from the bone marrow of p65 wild-type or knockout mice using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No technical replicates were performed.

2013-04-04 | E-GEOD-45755 | biostudies-arrayexpress

Gene expression in LPS stimulated IkappaB-beta knockout bone marrow derived macrophage (BMDM)

2010-06-09 | GSE22223 | GEO

The activation of IL-1 induced enhancers depends on TAK1 kinase activity and NF-KB p65 [RNA-Seq]

Project description:The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-?B subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-?B p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-?B-dependent enhancers in epithelial cells. RNA-seq of KB cells either untreated or treated with IL-1 alpha

2014-12-16 | E-GEOD-64185 | biostudies-arrayexpress

The activation of IL-1 induced enhancers depends on TAK1 kinase activity and NF-KB p65 [ChIP-Seq]

Project description:The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-κB subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-κB p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-κB-dependent enhancers in epithelial cells. ChIP-seq in KB cells with 5 different antibodies under different treatment conditions

2014-12-16 | E-GEOD-64223 | 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