Aspergillus fumigatus is a fungal pathogen that causes several invasive and noninvasive diseases named aspergillosis. This disease is generally regarded as multifactorial, considering that several pathogenicity determinants are present during the establishment of this illness. It is necessary to obtain an increased knowledge of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes. Protein phosphatases are essential to several signal transduction pathways. We identified 32 phosphatase catalytic subunit-encoding genes in A. fumigatus, of which we were able to construct 24 viable deletion mutants. The role of nine phosphatase mutants in the HOG (high osmolarity glycerol response) pathway was evaluated by measuring phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. We were also able to identify 11 phosphatases involved in iron assimilation, six that are related to gliotoxin resistance, and three implicated in gliotoxin production. These results present the creation of a fundamental resource for the study of signaling in A. fumigatus and its implications in the regulation of pathogenicity determinants and virulence in this important pathogen.
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http://dx.doi.org/10.1534/g3.115.016766 | DOI Listing |
Nat Commun
January 2025
Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Nuclear speckles are membraneless organelles that associate with active transcription sites and participate in post-transcriptional mRNA processing. During the cell cycle, nuclear speckles dissolve following phosphorylation of their protein components. Here, we identify the PP1 family as the phosphatases that counteract kinase-mediated dissolution.
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January 2025
Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud Universidad de Guadalajara, Guadalajara, Mexico.
Studies have noted the connection between Mycobacterium avium subspecies paratuberculosis (MAP) and autoimmunity. MAP is an intracellular pathogen that infects and multiplies in macrophages. To overcome the hostile environment elicited by the macrophage, MAP secretes a battery of virulence factors to neutralize the toxic effects of the macrophage.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia.
Background: Alzheimer's disease (AD) is a neurodegenerative disease that causes progressive cognitive decline over age 65. Individuals suffering from this disease suffer memory loss, and histological examination of the brains. Okadaic acid (OA), is a potent and selective inhibitor of protein phosphatases 1 and 2A.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Department of Bioinformatics and Systems Biology, MOE Key Laboratory of Molecular Biophysics, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Luoyu Road 1037, Wuhan, Hubei 430074, China.
Protein phosphorylation is dynamically and reversibly regulated by protein kinases and protein phosphatases, and plays an essential role in orchestrating a wide range of biological processes. Although a number of tools have been developed for predicting kinase-specific phosphorylation sites (p-sites), computational prediction of phosphatase-specific dephosphorylation sites remains to be a great challenge. In this study, we manually curated 4393 experimentally identified site-specific phosphatase-substrate relationships for 3463 dephosphorylation sites occurring on phosphoserine, phosphothreonine, and/or phosphotyrosine residues, from the literature and public databases.
View Article and Find Full Text PDFEur Rev Med Pharmacol Sci
December 2024
Department of Oral Biological and Medical Sciences, Faculty of Dentistry, The University of British Columbia, Vancouver, BC, Canada.
Objective: Monoamine oxidase (MAO) inhibitors reduce inflammation in a number of in vitro and in vivo models. This finding led to the development of a novel MAO-B selective inhibitor (RG0216) designed to reduce blood-brain barrier penetration. To elucidate RG0216's regulatory role in inflammation-relevant signaling pathways, we employed a transcriptome analytic approach to identify genes that are differentially regulated by RG0216 and then globally identified which inflammation-relevant biological signaling pathways were altered by this drug.
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