Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239796 | GEO | 2025/05/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [ChIP-seq]

Project description:We previously demonstrated that the NF-κB inhibitor IκBα binds the chromatin together with PRC2 to regulate a subset of developmental- and stem cell-related genes. This alternative function has been elusive in both physiological and disease conditions because of the predominant role of IκBα as a negative regulator of NF-κB. We here uniquely characterize specific residues of IκBα that allow the generation of separation-of-function (SOF) mutants that are defective for either NF-κBrelated (SOF DeltaNF-κB) or chromatin-related (SOF DeltaH2A,H4) activities. Expression of IκBα SOF DeltaNF-κB, but not SOF DeltaH2A/H4, is sufficient to negatively regulate a specific stemness program in intestinal cells, thus rescuing the differentiation blockage imposed by IκBα deficiency. . By ChIP assay we demonstrated IκBα binding to several stem cell genes that are transcriptionally repressed following IκBα SOF DeltaNF-κB induction. Our data indicate that SOF mutants represent an exclusive tool for studying IκBα functions in physiology and disease.

2025-05-18 | GSE271349 | GEO

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [RNA-Seq]

2025-05-18 | GSE206515 | GEO

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [RNAseq Knock-ins IKBa]

2025-05-18 | GSE292288 | GEO

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness

Project description:Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness

| PRJNA1000982 | ENA

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [RNA-Seq]

Project description:Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [RNA-Seq]

| PRJNA851251 | ENA

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [ChIP-seq]

Project description:Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [ChIP-seq]

| PRJNA1130975 | ENA

Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [RNAseq Knock-ins IKBa]

Project description:Separation-of-function mutants reveal the NF-κB-independent involvement of IκBα in the regulation of intestinal stemness [RNAseq Knock-ins IKBa]

| PRJNA1237823 | ENA

Histone deacetylase 4 inhibits NF-κB activation by facilitating IκBα sumoylation.

Project description:Protein modification by small ubiquitin-like modifier (SUMO) is an important regulatory mechanism for multiple cellular processes. Although the canonical pathway involving the ubiquitylation or phosphorylation of IκBα has been well characterized, little is known about the sumoylation of IκBα in the control of NF-κB activity. Here, we find that histone deacetylase 4 (HDAC4) negatively regulates tumor necrosis factor-alpha- or lipopolysaccharide-triggered NF-κB activation. HDAC4 belongs to the SUMO E3 ligase family and can directly sumoylate IκBα. The cytoplasm location of HDAC4 is essential for IκBα sumoylation. The Cys292 of HDAC4 is a key site for its SUMO E3 ligase activity. The sumoylation of IκBα prevents its polyubiquitination and degradation because these two modifications occur both at the Lys21. Our findings reveal a previously undiscovered role for HDAC4 in the inflammatory response as a SUMO E3 ligase for IκBα sumoylation. Our work provides insight into mechanisms ensuring optimal mediation of the NF-κB pathway.

| S-EPMC7948076 | biostudies-literature

Chlorogenic Acid Attenuates Oxidative Stress-Induced Intestinal Epithelium Injury by Co-Regulating the PI3K/Akt and IκBα/NF-κB Signaling.

Project description:Chlorogenic acid (CGA) is a natural polyphenol compound abundant in green plants with antioxidant and anti-inflammatory activities. Here, we explore its protective effects and potential mechanisms of action on intestinal epithelium exposure to oxidative stress (OS). We show that CGA attenuated OS-induced intestinal inflammation and injury in weaned pigs, which is associated with elevated antioxidant capacity and decreases in inflammatory cytokine secretion and cell apoptosis. In vitro study showed that CGA elevated phosphorylation of two critical signaling proteins of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway, Akt and nuclear factor erythroid-derived-related factor 2, leading to the elevated expression of intracellular antioxidant enzymes and heme oxygenase-1 (HO-1). Specific inhibition of HO-1 partially abolished its anti-inflammatory effect in IPEC-J2 cells exposure to OS. Interestingly, CGA suppressed the tumor necrosis factor-α (TNF-α) induced inflammatory responses in IPEC-J2 cells by decreasing phosphorylation of two critical inflammatory signaling proteins, NF-kappa-B inhibitor alpha (IκBα) and nuclear factor-κB (NF-κB). Specific inhibition of HO-1 cannot fully abolish its anti-inflammatory effect on the TNF-α-challenged cells. These results strongly suggested that CGA is a natural anti-inflammatory agent that can attenuate OS-induced inflammation and injury of intestinal epithelium via co-regulating the PI3K/Akt and IκBα/NF-κB signaling pathway.

| S-EPMC8750628 | biostudies-literature

Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages.

Project description:The nuclear factor κB (NF-κB) transcription factors coordinate the inflammatory immune response during microbial infection. Pathogenic substances engage canonical NF-κB signaling through the heterodimer RelA:p50, which is subjected to rapid negative feedback by inhibitor of κBα (IκBα). The noncanonical NF-κB pathway is required for the differentiation of immune cells; however, cross-talk between both pathways can occur. Concomitantly activated noncanonical signaling generates p52 from the p100 precursor. The synthesis of p100 is induced by canonical signaling, leading to the formation of the late-acting RelA:p52 heterodimer. This cross-talk prolongs inflammatory RelA activity in epithelial cells to ensure pathogen clearance. We found that the Toll-like receptor 4 (TLR4)-activated canonical NF-κB signaling pathway is insulated from lymphotoxin β receptor (LTβR)-induced noncanonical signaling in mouse macrophage cell lines. Combined computational and biochemical studies indicated that the extent of NF-κB-responsive expression of Nfkbia, which encodes IκBα, inversely correlated with cross-talk. The Nfkbia promoter showed enhanced responsiveness to NF-κB activation in macrophages compared to that in fibroblasts. We found that this hyperresponsive promoter engaged the RelA:p52 dimer generated during costimulation of macrophages through TLR4 and LTβR to trigger synthesis of IκBα at late time points, which prevented the late-acting RelA cross-talk response. Together, these data suggest that, despite the presence of identical signaling networks in cells of diverse lineages, emergent cross-talk between signaling pathways is subject to cell type-specific regulation. We propose that the insulation of canonical and noncanonical NF-κB pathways limits the deleterious effects of macrophage-mediated inflammation.

| S-EPMC5260935 | biostudies-literature

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