Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Activity-dependent COX-2 proteolysis

ABSTRACT: Cyclooxygenase-2 (COX-2) catalyzes the oxidation of arachidonic acid (AA) into a single product that is the source of all prostaglandins (PGs), ligands of multiple pro-inflammatory pathways. AA catalysis results in suicide inactivation, rendering the enzyme catalytically inactive. We report that catalytic activity also leads to controlled cleavage of COX-2, an event that is differentially regulated by fatty acids, and blocked by COX inhibitors. Using mass spectrometry, we identified two adjacent cleavage points within the catalytic domain, which give rise to COX-2 fragments that are catalytically inactive and localize to different cellular compartments. These fragments were also detected in human colon tumors. Expression of one of these fragments in cells significantly reduced mitochondrial function, increased lactate production, and enhanced proliferation.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Oded Kleifeld

LAB HEAD: Liza Barki-Harrington

PROVIDER: PXD057448 | Pride | 2024-11-25

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	2024-01-16-decoys-reviewed-contam-UP000005640.fas	Other
	2024-03-01-decoys-contam-UP000000589.fas	Other
	File_description	Other
	MF2_LFQ-MBR_human_semi.zip	Other
	MF4_LFQ-MBR_mouse_semi.zip	Other

Items per page:

1 - 5 of 17

Similar Datasets

Interaction between cyclooxygenase-2 and caspase-3 abolishes the cleavage of RNA-binding protein HuR and promotes drug resistance in oral squamous cell carcinoma

Project description:Here, we show that HuR cleavage is dependent on active caspase-3 in oral cancer cells treated with ionizing radiation and the chemotherapeutic drug paclitaxel. We determined that oral cancer cells overexpressing cyclooxygenase-2 (COX-2) limited the cleavage of both caspase-3 and HuR, which in turn, reduced the rate of apoptosis in paclitaxel treated cells. Specific inhibition of COX-2 by celecoxib promoted apoptosis through activation of caspase-3 and cleavage of HuR in paclitaxel-resistant oral cancer cells. In addition, oral cancer cells overexpressing cellular HuR increased the half-life of COX-2 mRNA and promoted COX-2 expression, exhibiting enhanced tumor growth in vivo in comparison with the cleavable form of HuR. Finally, our RNP IP and RNA transcriptome analysis of HuR under IR revealed that the HuR cleavage product-1 (HuR-CP1) associates and promotes the expression of mRNAs encoding proteins involved in apoptosis.

2017-02-14 | GSE79477 | GEO

Regioselective Protein Oxidative Cleavage Enabled by an Enzyme-like Recognition of an Inorganic Metal Oxo Cluster Ligand

Project description:Metal-catalyzed oxidation reactions (MCO) is one of the most applicable methods to induce protein oxidative modifications (e.g., protein oxidation, protein oxidative cleavage and crosslinking), which are essential techniques for many applications in biotechnology and redox proteomics. However, a suitable ligand is needed to assure high stability and enhance the metal catalytic efficiency in order to induce these oxidative modifications in a selective manner. Herein, we report the influence of the polyoxometalates (POMs) as inorganic ligands on the catalytic efficiency of Cu ions to induce oxidative cleavage of a protein. In the presence of ascorbic acid as (Asc), the Cu-substituted POM (Cu-POM), α2-K8P2W17O61(Cu2+.OH2), (CuWD), cleaved hen egg white lysozyme (HEWL), a protein consisting of 129 amino acids, producing only four peptide fragments. Analyzing the intact protein, in absence and presence of CuWD/Asc, and the peptide four peptide fragments via nLC-MS/MS revealed that CuWD/Asc induced oxidative modifications and cleavage at and/or near CuWD/HEWL binding sites

2023-01-30 | PXD037983 | Pride

Mouse ES cells expressing catalytically inactive Ring1B display impaired Ring1B and H3K27me3 deposition.

Project description:ChIP-seq for H3K27me3 and Ring1B was performed in WT mESCs and mESCs containing catalytically inactive Ring1B (I53A mutant). Cells expressing catalytically inactive Ring1B maintain the spatial distribution of Ring1B and H3K27me3 but at reduced levels. These findings support the notion that PRC2 recruitment is, in part, dependent on H2A ubiquitination (H2AK119ub). Two biological replicates were performed for Ring1B and H3K27me3 ChIPs in WT and Ring1B I53A/I53A mouse ESCs. Input chromatin was sequenced for each replicate as a control for ChIP enrichment.

2015-09-20 | E-GEOD-69955 | biostudies-arrayexpress

Eukaryote-Specific Insertion Elements Control Human ARGONAUTE Slicer Activity

Project description:We solved the crystal structure of human ARGONAUTE1 (hAGO1) bound to endogenous 5'-phosphorylated guide RNAs. To identify structural changes that evolutionarily rendered hAGO1 inactive, we compared our structure with published structures of guide-RNA-containing and cleavage-active hAGO2. Aside from mutation of a catalytic tetrad residue, proline residues at positions 670 and 675 in hAGO1 introduce a kink in the cS7 loop and thereby forming a convex surface within the hAGO1 nucleic-acid-binding channel near the inactive catalytic site. We predicted that even upon restoration of the catalytic tetrad, hAGO1-cS7 sterically hinders the placement of a fully-paired guide-target RNA duplex into the endonuclease active site. Consistent with this hypothesis, reconstitution of the catalytic tetrad (R805H) led to low level hAGO1 cleavage activity, whereas combining R805H with cS7 substitutions (P670S and P675Q) substantially augmented hAGO1 activity. Evolutionary changes to hAGO1 were subtle and readily reversible, suggesting that loading of guide RNA and seed-based miRNA-target RNA pairing constrain its sequence drift. Structure-guided design of mutations that confer slicer activity to hAGO1. RNAs were isolated from recombinant purified hAGO1 and hAGO2, processed from baculovirus-infected Trichoplusia ni insect cells, and then processed for Illumina HiSeq. In addition, total RNA samples from AGO1 baculouvirus infected vs. non-infected Trichoplusia ni cells were isolated and also processed for Illumina HiSeq.

2013-06-20 | E-GEOD-48076 | biostudies-arrayexpress

Regulation of cellular proteome and acetylome by catalytic and non-catalytic functions of class I histone deacetylases

Project description:Project description: Taking advantage of a newly generated model system, we examined the influence of class I HDAC catalytic and non-catalytic function on the cellular proteome and acetylome. Therefore, we generated HAP1 cell lines either lacking individual class I HDACs or expressing catalytically inactive isoforms. Using these cell lines, we investigated whether deletion or inactivation of specific class I HDACs better mimics inhibitor treated cells using isobaric labeling (TMTpro).

2022-08-16 | PXD030164 | Pride

Eukaryote-Specific Insertion Elements Control Human ARGONAUTE Slicer Activity

2013-06-20 | GSE48076 | GEO

Inhibition of mPGES-1 or COX-2 Results in Different Proteomic and Lipidomic Profiles in A549 Lung Cancer Cells

Project description:We compared the effects of mPGES-1 inhibitor Compound III (CIII) with the cyclooxygenase (COX)-2 inhibitor NS-398 on protein and lipid profiles in interleukin (IL)-1β induced A549 lung cancer cells using mass spectrometry. Inhibition of mPGES-1 decreased PGE2 production and increased PGF2α and thromboxane B2 (TXB2) formation, while inhibition of COX-2 decreased the production of all three prostanoids. Our proteomics results revealed that CIII downregulated multiple canonical pathways including eIF2, eIF4/P70S6K, and mTOR signaling, compared to NS-398 that activated these pathways.

2019-05-20 | PXD013490 | Pride

Clinical study of the effect of combined treatment of aspirin and zileuton on biomarkers of tobacco-related carcinogenesis in current smokers

Project description:A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-LOX inhibitor has single agent activity and adds to the activity of NSAIDs in preclinical models of tobacco carcinogenesis We hypothesized that COX inhibitor + 5-LOX inhibitor may be more effective than placebo in modulating nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low dose ASA plus zileuton vs. double placebo in current smokers to compare modulating effects on nasal epithelium gene expression and arachidonic acid (AA) metabolism. Sixty-three participants were randomized to combined treatment of ASA (81 mg QD) and zileuton (Zyflo CR) two 600 mg extended release tablets BID or placebo pills for 12 weeks. Combined ASA plus zileuton had minimal effects on nasal gene expression of nasal or bronchial gene expression signatures associated with smoking, lung cancer and chronic obstructive pulmonary disease but did favorably modulate a bronchial gene signature of squamous dysplasia. Combined ASA plus zileuton suppressed urinary leukotriene (LTE4) (change of 89.867±68.35 from baseline to 32.25±23.25, p <0.001), a surrogate of 5-LOX mediated AA metabolism but did not suppress urinary prostaglandin E2 metabolite (PGEM), a surrogate of cyclooxygenase-mediated AA metabolism. In conclusion, combined COX and 5-LOX inhibition by combined low dose ASA with zileuton in smokers favorably modulated a bronchial squamous dysplasia gene expression signature in the nasal epithelium of current smokers but had minimal effects on other carcinogenesis gene signatures. This combination decreased 5-LOX but not COX-2 mediated AA metabolism. Nasal gene expression signature determination is a novel approach to biomarker analysis, giving an approximation of the pulmonary milieu without having to perform invasive tissue sampling.

2022-06-29 | GSE175616 | GEO

Identifying cleaved and noncleaved targets of small interfering RNAs and microRNAs in mammalian cells by SpyCLIP

Project description:we report a strategy to establish a comprehensive picture of siRNA cleaved and noncleaved off-targets by performing SpyCLIP using wild-type and catalytically inactive AGO2 mutants in parallel. Additionally, we investigated naturally occurring cleavage events mediated by endogenous miRNAs using the same strategy. Our results demonstrated that AGO2 SpyCLIP is a powerful method to identify both cleaved and noncleaved targets of siRNAs, providing valuable information for improving siRNA design rules

2020-12-01 | GSE145438 | GEO

A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity

Project description:Here we identify a Dicer-independent miRNA biogenesis pathway that employs the slicer catalytic activity of Argonaute2 (Ago2). To uncover Dicer-independent miRNAs, we sequenced small RNAs in wild type, maternal-zygotic dicer (MZdicer) and MZago2 mutants, using zebrafish as a model system. We find that, in contrast to other miRNAs, miR-451 levels were increased in MZdicer but drastically reduced in the MZago2 mutants. We show that pre-miR-451 processing requires Ago2 catalytic activity in vivo. MZago2 mutant embryos display delayed erythrocyte maturation that can be rescued by wild type Ago2 or miR-451 duplex but not catalytically dead Ago2. We propose that Ago2-mediated cleavage of a subset of pre-miRNAs, followed by uridylation and trimming, generates functional miRNAs in a Dicer-independent manner. Examination of small RNAs (18 to 35 nucleotides) in 3 different zebrafish genotypes (wild type, MZago2, MZdicer) at 48 hours post-fertilization.

2010-07-01 | E-GEOD-21503 | biostudies-arrayexpress