Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neurological defects in CAIX knockout mice

ABSTRACT: To further identify transcriptomic responses to CAIX deficiency in the brain, genome-wide cDNA microarray analyses were performed. Thirty-one and 37 genes were up- and down-regulated in the brain of Car9-/- mice as compared to wild-type mice. Functional annotation revealed that genes with increased expression are mainly involved in alternative splicing, nucleotide binding, RNA binding, and regulation of cellular protein metabolic process; whereas genes with reduced expression are chiefly implicated in cellular cation homeostasis, positive regulation of ion transport, Ubl conjugation, phosphorus metabolic process, and regulation of cell proliferation. Notably, the biological processes behaviour and locomotory behaviour are two prominent over-representation terms among the down-regulated genes, which is consistent with the results obtained from behavioural tests.

ORGANISM(S): Mus musculus

PROVIDER: GSE24051 | GEO | 2011/12/31

SECONDARY ACCESSION(S): PRJNA130253

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Neurological defects in CAIX knockout mice

Project description:To further identify transcriptomic responses to CAIX deficiency in the brain, genome-wide cDNA microarray analyses were performed. Thirty-one and 37 genes were up- and down-regulated in the brain of Car9-/- mice as compared to wild-type mice. Functional annotation revealed that genes with increased expression are mainly involved in alternative splicing, nucleotide binding, RNA binding, and regulation of cellular protein metabolic process; whereas genes with reduced expression are chiefly implicated in cellular cation homeostasis, positive regulation of ion transport, Ubl conjugation, phosphorus metabolic process, and regulation of cell proliferation. Notably, the biological processes behaviour and locomotory behaviour are two prominent over-representation terms among the down-regulated genes, which is consistent with the results obtained from behavioural tests. Brain tissue samples were collected from five wild-type and four CAIX KO mice, respectively, at the age of eight months. Total RNAs were purified and used for cDNA microarray.

2011-12-31 | E-GEOD-24051 | biostudies-arrayexpress

MS/MS analysis of Ub-conjugated UbcH7 ubiquitination sites

Project description:By conducting the ubiquitin-conjugation assay for UbcH7, we found that PknG was able to promote the loading of Ub onto UbcH7, which is indicated by a molecular weight shift in SDS–PAGE. The classic Ub conjugation of E2s requires the E1 to form a thiol-ester bond between its active Cys and the C-terminal Gly of Ub. Notably, PknG could directly catalyze Ub conjugation onto UbcH7 in a kinase activity-independent and Ubl domain-dependent manner.

2021-04-16 | PXD020982 | Pride

E2/E3-independent ubiquitin-like protein conjugation by Urm1 is directly coupled to cysteine persulfidation

Project description:Posttranslational modifications by ubiquitin-like proteins (UBL) are essential for nearly all cellular processes. Ubiquitin related modifier 1 (Urm1) is a non-canonical UBL which plays a key role in tRNA anticodon thiolation as a sulfur carrier protein (SCP). While Urm1 has also been observed to conjugate directly to target proteins like other UBLs, the mechanism of attachment as well as how the SCP properties of Urm1 may impact its conjugation are unknown. Here, we reconstitute the covalent attachment of Urm1 to various cellular target proteins in vitro, revealing that, unlike other known UBLs, this process is E2/E3-independent and requires oxidative stress conditions. We determined the crystal structures of the peroxiredoxin Ahp1 before and after covalent attachment of Urm1. Strikingly, we show that this conjugation process results in persulfidation of a cysteine residue in the target protein. Demonstrating that Urm1 actively transfers sulfur atoms to proteins as part of its conjugation reaction. Our results redefine Urm1 as a key evolutionary link between prokaryotic SCPs and the plethora of UBL modifications observed in modern eukaryotes, and demonstrate a critical role for Urm1 in protecting proteins during oxidative stress.

2021-11-16 | MSV000088390 | MassIVE

Inhibition of pH regulation as a therapeutic strategy in hypoxic human breast cancer cells

Project description:Experiments were performed assessing whether targeting the pH regulatory proteins (CAIX, NHE1 and V-ATPase) that permit cancer cells to adapt to hypoxic conditions could produce an effective therapeutic response in breast cancer, using both 2D and 3D culture models. CAIX inhibitors were shown to combine effectively with irradiation in clonogenic assays. Proteomic-mass-spectrometric analysis was carried out to analyze the possible mechanisms through which the CAIX inhibitor used was combining with irradiation.

2017-05-02 | PXD005706 | Pride

pre-mRNA splicing in C. elegans

Project description:To study pre-mRNA splicing function of the ubiquitin-like protein Hub1/UBL-5 in Caenorhabditis elegans. We have employed splicing-sensitive microarray expression profiling to examine the changes in pre-mRNA splicing. We collected wild-type and ubl-5 knock out worms at L3 stage and isolated total RNA. Which was reverse transcribed to double-stranded cDNA and cRNA was generated by in vitro transcription. The labeled cRNA samples were fragmented at 60°C and hybridized on to an Agilent Gene Expression Microarray. The data showed accumulation of intron- and outron containing transcripts in ubl-5 knockout worms in comparison to wild-type worms

2022-11-02 | GSE157943 | GEO

Critical role of the UBL-domain in stimulating the E3 ubiquitin ligase activity of UHRF1 towards chromatin

Project description:The RING E3 ubiquitin ligase UHRF1 controls DNA methylation through its ability to target the maintenance DNA methyltransferase DNMT1 to newly replicated chromatin. DNMT1 recruitment relies on ubiquitylation of histone H3 by UHRF1, however, how UHRF1 deposits ubiquitin onto the histone is unknown. Here, we demonstrate that the ubiquitin-like domain (UBL) of UHRF1 is essential for RING-mediated H3 ubiquitylation. Using chemical crosslinking and mass spectrometry, biochemical assays and recombinant chromatin substrates we show that the UBL participates in structural rearrangements of UHRF1 upon binding to chromatin and the E2 ubiquitin conjugating enzyme UbcH5a/UBE2D1. Similar to ubiquitin, the UBL exerts its effects through a hydrophobic patch that contacts a regulatory surface on the “backside” of the E2 to stabilise the E2-E3-chromatin complex. Our analysis of the enzymatic mechanism of UHRF1 uncovers an unexpected function of the UBL-domain and defines a new role for this domain in DNMT1-dependent inheritance of DNA methylation.

2018-08-29 | GSE119120 | GEO

Impact of SLC-0111 (U-104) on HUH6 hepatoblastoma cell transcriptome in normoxic and hypoxic conditions

Project description:Carbonic anhydrase 9 (CAIX) is a transmembrane metalloenzyme whose main function is to maintain the acid-base balance of the cell and hypoxic condition induces its expression. Solid tumors often exhibit regions with low oxygen content in areas where the blood supply is insufficient. CAIX is overexpressed in multiple solid tumors, including hepatoblastoma, the most frequent childhood liver malignancy. SLC-0111 is a commercially available CAIX inhibitor that is currently passed Phase I clinical trial on solid tumors. In this study we assessed the impact of SLC-0111 on transcriptomic changes of HUH6 hepatoblastoma cell line cells in both normoxic and hypoxic condition.

2022-04-30 | GSE185937 | GEO

Project description:Conjugation of multiresistance genes enhanced by carbamazepine

| PRJNA445362 | ENA

Genome-wide synthetic lethal screen unveils novel CAIX – NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors.

Project description:Hypoxia is an important clinicopathological feature of solid tumours that limits response to therapy. Carbonic Anhydrase IX (CAIX) is a hypoxia-induced, pH regulator that has emerged as a viable therapeutic target. Targeting CAIX has demonstrated promise in difficult to treat preclinical models of breast pancreatic, melanoma and brain cancers when combined with chemotherapy and immunotherapy, however resistance ultimately develops and this mechanism is unclear. Here we used an unbiased genome-wide synthetic lethal CRISPR knock-out screen in basal breast cancer cells to identify co-vulnerabilities and mechanisms of compensation for CA9 loss. We identified a redox homeostasis network containing thioredoxin and the iron-sulfur cluster enzyme, cysteine desulfurase, NFS1, indicative of the critical importance of CAIX in this role.

2021-08-28 | GSE167481 | GEO

Impaired locomotor behavior of C. elegans neuroligin mutants is dependent of the catechol-O-methyltransferase COMT-4

Project description:Neuroligins are neuronal membrane adhesion molecules that have been involved in neuro-psychiatric and neuro-developmental disorders. They interact with neurexins and other specific proteins in the synaptic cleft. The nlg-1 gene of Caenorhabditis elegans encodes NLG-1, an ortholog of human neuroligins. NLG-1 is involved in dopaminergic and serotoninergic signaling that controls the locomotory rate of the nematode. When well fed animals are transferred to a plate with food (bacterial lawn) they reduce the locomotory rate. This behavior, which depends on dopamine, is known as basal slowing response (BSR). Alternatively, food deprived animals when moved to a plate with a bacterial lawn, further decrease their locomotory rate. This behavior, known as enhanced slowing response (ESR) is serotonin dependent. C. elegans nlg-1- deficient mutants are impaired in BSR, ESR and other locomotory behaviors such as gentle touch response. Here we report that nlg-1 mutants upregulate the expression of comt-4 which encodes an enzyme that presumably has catechol-O-methyltransferase activity involved in dopamine degradation. Our study also shows that comt-4(RNAi) in nlg-1-deficient mutants recovers wild type phenotypes of BSR, ESR and gentle touch responses. Based on these results we propose a model for the neuroligin function in modulating the dopamine-dependent locomotory behavior in the nematode.

2018-05-31 | GSE97980 | GEO

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