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DDI2 protease controls embryonic development and inflammation via TCF11/NRF1

dc.contributor.authorNedomová, Monika
dc.contributor.authorHaberecht-Müller, Stefanie
dc.contributor.authorMöller, Sophie
dc.contributor.authorVenz, Simone
dc.contributor.authorProcházková, Michaela
dc.contributor.authorProcházka, Jan
dc.contributor.authorSedlák, František
dc.contributor.authorChawengsaksophak, Kallayanee
dc.contributor.authorHammer, Elke
dc.contributor.authorKašpárek, Petr
dc.contributor.authorAdámek, Michael
dc.contributor.authorSedláček, Radislav
dc.contributor.authorKonvalinka, Jan
dc.contributor.authorElke, Kruger
dc.contributor.authorGrantz Šašková, Klára
dc.date.accessioned2024-10-09T09:45:52Z
dc.date.available2024-10-09T09:45:52Z
dc.date.issued2024
dc.identifier.urihttps://hdl.handle.net/20.500.14178/2650
dc.description.abstractDDI2 is an aspartic protease that cleaves polyubiquitinated substrates. Upon proteotoxic stress, DDI2 activates the transcription factor TCF11/NRF1 (NFE2L1), crucial for maintaining proteostasis in mammalian cells, enabling the expression of rescue factors, including proteasome subunits. Here, we describe the consequences of DDI2 ablation in vivo and in cells. DDI2 knock-out (KO) in mice caused embryonic lethality at E12.5 with severe developmental failure. Molecular characterization of embryos showed insufficient proteasome expression with proteotoxic stress, accumulation of high molecular weight ubiquitin conjugates and induction of the unfolded protein response (UPR) and cell death pathways. In DDI2 surrogate KO cells, proteotoxic stress activated the integrated stress response (ISR) and induced a type I interferon (IFN) signature and IFN-induced proliferative signaling, possibly ensuring survival. These results indicate an important role for DDI2 in the cell-tissue proteostasis network and in maintaining a balanced immune response.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1016/j.isci.2024.110893
dc.rightsCreative Commons Uveďte původ-Neužívejte dílo komerčně 4.0 Internationalcs
dc.rightsCreative Commons Attribution-NonCommercial 4.0 Internationalen
dc.titleDDI2 protease controls embryonic development and inflammation via TCF11/NRF1en
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by-nc/4.0/legalcode
dc.date.updated2025-02-13T14:11:21Z
dc.subject.keywordDDI2 proteaseen
dc.subject.keywordproteasomeen
dc.subject.keywordubiquitinen
dc.subject.keywordubiquitin proteaseen
dc.subject.keywordTCF11/NRF1en
dc.subject.keywordNFE2L1en
dc.subject.keywordknock-outen
dc.subject.keywordinterferonen
dc.subject.keywordbZIP transcription factoren
dc.subject.keywordtank-binding kinase-1en
dc.identifier.eissn2589-0042
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//PRIMUS/21/SCI/018
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/MSM//SVV260679
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/GA0/GA/GA22-16389S
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/COOP/COOP
dc.date.embargoStartDate2025-02-13
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.isci.2024.110893
dc.identifier.utWos001318582000001
dc.identifier.eidScopus2-s2.0-85207346406
dc.identifier.obd652436
dc.identifier.pubmed39328932
dc.subject.rivPrimary10000::10600
dcterms.isPartOf.nameiScience
dcterms.isPartOf.issn2589-0042
dcterms.isPartOf.journalYear2024
dcterms.isPartOf.journalVolume27
dcterms.isPartOf.journalIssue10
uk.faculty.primaryId108
uk.faculty.primaryName1. lékařská fakultacs
uk.faculty.primaryNameFirst Faculty of Medicineen
uk.faculty.secondaryId115
uk.faculty.secondaryNamePřírodovědecká fakultacs
uk.faculty.secondaryNameFaculty of Scienceen
uk.department.primaryId108
uk.department.primaryName1. lékařská fakultacs
uk.department.primaryNameFirst Faculty of Medicineen
uk.department.secondaryId1492
uk.department.secondaryId1034
uk.department.secondaryNameÚstav biochemie a experimentální onkologie 1. LF UKcs
uk.department.secondaryNameInstitute of Biochemistry and Experimental Oncologyen
uk.department.secondaryNameKatedra genetiky a mikrobiologiecs
uk.department.secondaryNameDepartment of Genetics and Microbiologyen
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleDDI2 protease controls embryonic development and inflammation via TCF11/NRF1en


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