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dc.contributor.authorPaquette, Nicholas Paul
dc.contributor.authorConlon, Joseph E.
dc.contributor.authorSweet, Charles R.
dc.contributor.authorRus, Florentina
dc.contributor.authorWilson, Lindsay
dc.contributor.authorPereira, Andrea J.
dc.contributor.authorRosadini, Charles V.
dc.contributor.authorGoutagny, Nadege
dc.contributor.authorWeber, Alexander N. R.
dc.contributor.authorLane, William S.
dc.contributor.authorShaffer, Scott A.
dc.contributor.authorManiatis, Stephanie
dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorStuart, Lynda M.
dc.contributor.authorSilverman, Neal S.
dc.date2022-08-11T08:09:08.000
dc.date.accessioned2022-08-23T16:18:53Z
dc.date.available2022-08-23T16:18:53Z
dc.date.issued2012-07-31
dc.date.submitted2013-01-31
dc.identifier.citationProc Natl Acad Sci U S A. 2012 Jul 31;109(31):12710-5. doi: 10.1073/pnas.1008203109. <a href="http://dx.doi.org/10.1073/pnas.1008203109" target="_blank">Link to article on publisher's site</a>
dc.identifier.issn0027-8424 (Linking)
dc.identifier.doi10.1073/pnas.1008203109
dc.identifier.pmid22802624
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34919
dc.descriptionThis article contains supporting information online at <a href="http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1008203109/-/DCSupplemental" target="_blank">www.pnas.org/lookup/suppl/doi:10.1073/pnas.1008203109/-/DCSupplemental</a>.
dc.description.abstractThe Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-kappaB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-kappaB signaling pathway (IMD) but not the other (Toll). In fact, we show YopJ mediated serine/threonine acetylation and inhibition of dTAK1, the critical MAP3 kinase in the IMD pathway. Acetylation of critical serine/threonine residues in the activation loop of Drosophila TAK1 blocks phosphorylation of the protein and subsequent kinase activation. In addition, studies in mammalian cells show similar modification and inhibition of hTAK1. These data present evidence that TAK1 is a target for YopJ-mediated inhibition.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=22802624&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsPublisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.
dc.subjectAcetylation
dc.subjectAnimals
dc.subjectBacterial Proteins
dc.subjectDrosophila melanogaster
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subject*Immunity, Innate
dc.subjectMAP Kinase Kinase Kinases
dc.subject*MAP Kinase Signaling System
dc.subjectNF-kappa B
dc.subjectPlague
dc.subjectSerine O-Acetyltransferase
dc.subjectYersinia pestis
dc.subjectImmunology and Infectious Disease
dc.titleSerine/threonine acetylation of TGFbeta-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume109
dc.source.issue31
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1143&amp;context=infdis_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/144
dc.identifier.contextkey3631084
refterms.dateFOA2022-08-23T16:18:53Z
html.description.abstract<p>The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-kappaB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-kappaB signaling pathway (IMD) but not the other (Toll). In fact, we show YopJ mediated serine/threonine acetylation and inhibition of dTAK1, the critical MAP3 kinase in the IMD pathway. Acetylation of critical serine/threonine residues in the activation loop of Drosophila TAK1 blocks phosphorylation of the protein and subsequent kinase activation. In addition, studies in mammalian cells show similar modification and inhibition of hTAK1. These data present evidence that TAK1 is a target for YopJ-mediated inhibition.</p>
dc.identifier.submissionpathinfdis_pp/144
dc.contributor.departmentProteomics and Mass Spectrometry Facility, Department of Biochemistry and Molecular Pharmacology
dc.contributor.departmentDepartment of Department of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages12710-5


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