USP2 inhibition prevents infection with ACE2- dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE237741 | GEO | 2023/12/08
REPOSITORIES: GEO
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Project description:USP2 inhibition prevents infection with ACE2- dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice
| PRJNA996524 | ENA
Project description:Ubiquitylation plays an important role in the control of Na+ homeostasis by the kidney. It is well established that the epithelial Na+ channel ENaC is regulated by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression and activity. Ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs). One such DUB, USP2-45, was identified previously as an aldosterone-induced protein in the kidney, and is also a circadian output gene. In heterologous expression systems USP2-45 binds to ENaC, deubiquitylates it and enhances channel density and activity at the cell surface. Because the role of USP2-45 in renal Na+ transport had not been studied in vivo, we investigated here the effect of Usp2 gene inactivation in this process. We demonstrate first that the USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did not show any differences to wild-type littermates with respect to the diurnal control of Na+ or K+ urinary excretion and plasma levels neither on standard diet, nor after acute and chronic changes to low and high Na+ diets, respectively. Moreover, they had similar aldosterone levels either at low or high Na+ diet. Blood pressure measurements using telemetry did not reveal variations as compared to control mice. Usp2-KO did neither display alternations in ENaC or Na+,Cl--cotransporter (NCC) expression, nor were there any changes in regulatory protein levels, as evidenced by immunoblotting and transcriptome analysis. We conclude that USP2-45 is not crucial for the regulation of Na+ balance or maintenance of blood pressure in vivo.
2013-01-16 | GSE43517 | GEO
Project description:Ubiquitylation plays an important role in the control of Na+ homeostasis by the kidney. It is well established that the epithelial Na+ channel ENaC is regulated by the ubiquitin-protein ligase NEDD4-2, limiting ENaC cell surface expression and activity. Ubiquitylation can be reversed by the action of deubiquitylating enzymes (DUBs). One such DUB, USP2-45, was identified previously as an aldosterone-induced protein in the kidney, and is also a circadian output gene. In heterologous expression systems USP2-45 binds to ENaC, deubiquitylates it and enhances channel density and activity at the cell surface. Because the role of USP2-45 in renal Na+ transport had not been studied in vivo, we investigated here the effect of Usp2 gene inactivation in this process. We demonstrate first that the USP2-45 protein has a rhythmic expression with a peak at ZT12. Usp2-KO mice did not show any differences to wild-type littermates with respect to the diurnal control of Na+ or K+ urinary excretion and plasma levels neither on standard diet, nor after acute and chronic changes to low and high Na+ diets, respectively. Moreover, they had similar aldosterone levels either at low or high Na+ diet. Blood pressure measurements using telemetry did not reveal variations as compared to control mice. Usp2-KO did neither display alternations in ENaC or Na+,Cl--cotransporter (NCC) expression, nor were there any changes in regulatory protein levels, as evidenced by immunoblotting and transcriptome analysis. We conclude that USP2-45 is not crucial for the regulation of Na+ balance or maintenance of blood pressure in vivo. We compared gene expression in kidneys from Usp2 Knock-Out versus Wild-Type. Six pairs of male littermates Usp2-KO and WT were combined in two pools per condition (3 animals per pool) keeping the littermate pairing between pools.
2013-01-16 | E-GEOD-43517 | biostudies-arrayexpress
Project description:The homologous Ace2 and Swi5 transcription factors of Saccharomyces cerevisiae have identical DNA-binding domains, and both are cell cycle regulated. There are common target genes, as well as genes activated only by Ace2 and other genes activated only by Swi5. Keywords: genetic modification RNA was isolated from four strains: wild type, ace2 gene deletion, swi5 gene deletion, and the ace2 swi5 double gene deletion. RNAs from the three mutant strains were compared to wild type RNA in a microarray hybridization experiment.
2008-05-13 | E-GEOD-11380 | biostudies-arrayexpress
Project description:Renal transcriptome analysis of Usp2 knockout mice. Please note 'Zeitgeber time 12' means 12 hours after light onset in 12h: light 12h dark housing conditions. It is of importance in the present design because of the strong circadian oscillation of the interest gene. In the Characteristics[genetic modification] column Usp2-Lac0-SA-IRES-lacZ-WT Neo/Kan is the name of the targeting cassette which was inserted in the gene, in opposition to non for the WT who carry no mutation.
2013-03-20 | E-MTAB-1442 | biostudies-arrayexpress
Project description:So far, we have found PMA induced USP2b isoform in myeloid leukemia cell lines such as HL60, THP-1, and U937. To explore molecular function of USP2 in the cells, we assess expression profiles of HL60-derivatives continuously expressing shRNA for USP2 and control shRNA.
2013-08-27 | GSE20476 | GEO
Project description:The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency, and no approved therapeutics or vaccines are currently available. The viral spike protein S binds membrane-tethered ACE2 on host cells in the lungs to initiate molecular events that ultimately release the viral genome intracellularly. The extracellular protease domain of ACE2 inhibits cell entry of both SARS and SARS-2 coronaviruses by acting as a soluble decoy for receptor binding sites on S, and is a promising candidate for therapeutic and prophylactic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S at a cell surface. Mutations are found across the protein-protein interface and also at buried sites where they are predicted to enhance folding and presentation of the interaction epitope. The mutational landscape offers a preliminary blueprint for engineering high affinity ACE2 receptors to meet this unprecedented challenge.
2020-03-19 | GSE147194 | GEO
Project description:BMPR2 mutation causes pulmonary arterial hypertension (PAH); ACE2 treatment can resolve established BMPR2-mediated PAH. The purpose of this study was to uncover the molecular mechanism behind this. Four groups: +/- ACE2 and +/- BMPR2 transgene, two arrays each, each array a pool of three animals.
2010-08-24 | E-GEOD-21583 | biostudies-arrayexpress
Project description:So far, we have found PMA induced USP2b isoform in myeloid leukemia cell lines such as HL60, THP-1, and U937. To explore molecular function of USP2 in the cells, we assess expression profiles of HL60-derivatives continuously expressing shRNA for USP2 and control shRNA. HL60 derivatives continuously expressing shRNA for USP2 and control shRNA were treated with PMA (30nM) for 0, 1, 2, and 3 days. Total RNA was extracted from the cells and subjected to microarray experiments using Human Genome U133 GeneChips.
2013-08-27 | E-GEOD-20476 | biostudies-arrayexpress