Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of p65 palmitoylation on gene expression when overexpressing vector or p65 WT or p65 2CS in p65 knockout 293A cells combined with TNFα treatment

ABSTRACT: Nuclear factor kappa B (NF-κB) is a central regulator of inflammation, infection, and immunity pathways and is often dysregulated in autoimmune diseases, inflammatory disorders, and cancers. However, the mechanisms by which different stimuli, including cellular metabolism, modulate NF-κB activation remain unclear. Here, we report that RelA ( p65), a major component of NF-κB, is S-palmitoylated at cysteine 197 and 206 by directly reacting with palmitoyl-CoA. Autopalmitoylation of p65 promotes its nuclear localization and p65-p50 complex formation, thereby enhancing NF-κB transcriptional activities. Furthermore, p65 palmitoylation upregulates RelB expression and promotes non-canonical NF-κB complex formation, further amplifying pathway activation. We also demonstrate that a high-fat diet could enhance p65 palmitoylation and correlate with an increased cytokine production in mouse tissues. These results reveal that lipid metabolism might directly regulate NF-κB activity and suggest that targeting p65 auto-palmitoylation could be a potential therapeutic strategy for diseases with deregulated NF-κB pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286561 | GEO | 2025/01/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Flotillin-1 palmitoylation is essential for its stability and subsequent tumor promoting capabilities.

Project description:Flotillin-1 contributes to invasion and metastasis in triple negative breast cancer (TNBC). Palmitoylation, the process of conjugating palmitoyl-CoA to proteins, plays an essential role in protein stability and trafficking. Flotillin-1 is modified by palmitoylation, however, the role of its palmitoylation in the context of metastasis has not been explored. Using palmitoylation defective flotillin-1 constructs, we have demonstrated that flotillin-1 palmitoylation contributes to its stability and metastatic capabilities in vivo. Further investigation led to the identification of zDHHC5 as the main palmitoyl acyl transferase responsible for palmitoylating flotillin-1, which also contributed to its stability by preventing its poly-ubiquitylation. To assess the ability to target flotillin-1 palmitoylation therapeutically, we designed a competitive peptide, which displayed efficacy in blocking flotillin-1 palmitoylation in vitro without altering palmitoylation of other zDHHC5 substrates, highlighting its specificity. Additionally, multiple TNBC tumor models expressing a doxycycline inducible flotillin-1 palmitoylation inhibiting peptide construct displayed attenuated tumor growth and lung metastasis. The current study has demonstrated the palmitoylation of flotillin-1, a known metastasis inducing protein, to be essential for its protein stability. The demonstrated methods in blocking its palmitoylation through the delivery of a competitive peptide provide proof-of-concept data for further development as a potential targeted therapeutic in TNBC.

2024-03-15 | GSE236971 | GEO

Dynamic Palmitoylation Events Following T-Cell Receptor Signaling

Project description:Palmitoylation is the reversible addition of palmitate to cysteine via a thioester linkage. The reversible nature of this modification makes it a prime candidate as a mechanism for regulating signal transduction in T-cell receptor signaling. Following stimulation of the T-cell receptor we find a number of proteins are newly palmitoylated, including those involved in vesicle-mediated transport and Ras signal transduction. Among these stimulation-dependent palmitoylation targets are the v-SNARE VAMP7, important for docking of vesicular LAT during TCR signaling, and the largely undescribed palmitoyl acyltransferase DHHC18 that is expressed in two isoforms in T cells. Using our newly developed On-Plate Palmitoylation Assay (OPPA), we show DHHC18 is capable of palmitoylating VAMP7 at Cys183. Cellular imaging shows that the palmitoylation-deficient protein fails to be retained at the Golgi.

2021-09-09 | PXD018703 | Pride

Palmitoylation negatively regulates AEG-1 function

Project description:In vitro studies revealed that AEG-1 is palmitoylated at cysteine at a.a. 75 position. In order to check how palmitoylation regulates AEG-1 function in vivo we generated a knockin moue using CRISPR/Cas9 taking in which cysteine 75 was mutated to serine (AEG-1-C75S). Hepatocytes were isolated from AEG-1-WT and AEG-1C75S littermates, total RNA was isolated and RNA-sequencing was performed.

2023-01-25 | GSE215113 | GEO

Dynamic Palmitoylation Events Following T-Cell Receptor Signaling

2021-09-09 | PXD018710 | Pride

Effects of p65 palmitoylation on gene expression when overexpressing vector or p65 WT or p65 2CS in p65 knockout 293A cells combined with TNFα treatment

Project description:Effects of p65 palmitoylation on gene expression when overexpressing vector or p65 WT or p65 2CS in p65 knockout 293A cells combined with TNFα treatment

| PRJNA1209914 | ENA

The activation of IL-1-induced enhancers depends on TAK1 kinase activity and NF-kappaB p65 II

2014-12-17 | GSE64237 | GEO

The activation of IL-1-induced enhancers depends on TAK1 kinase activity and NF-kappaB p65 I

2014-12-17 | GSE64201 | GEO

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

2014-12-16 | GSE64185 | GEO

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

2014-12-16 | GSE64223 | GEO