dc.contributor.author | Nedomová, Monika | |
dc.contributor.author | Haberecht-Müller, Stefanie | |
dc.contributor.author | Möller, Sophie | |
dc.contributor.author | Venz, Simone | |
dc.contributor.author | Procházková, Michaela | |
dc.contributor.author | Procházka, Jan | |
dc.contributor.author | Sedlák, František | |
dc.contributor.author | Chawengsaksophak, Kallayanee | |
dc.contributor.author | Hammer, Elke | |
dc.contributor.author | Kašpárek, Petr | |
dc.contributor.author | Adámek, Michael | |
dc.contributor.author | Sedláček, Radislav | |
dc.contributor.author | Konvalinka, Jan | |
dc.contributor.author | Elke, Kruger | |
dc.contributor.author | Grantz Šašková, Klára | |
dc.date.accessioned | 2024-10-09T09:45:52Z | |
dc.date.available | 2024-10-09T09:45:52Z | |
dc.date.issued | 2024 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14178/2650 | |
dc.description.abstract | DDI2 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.iso | en | |
dc.relation.url | https://doi.org/10.1016/j.isci.2024.110893 | |
dc.rights | Creative Commons Uveďte původ-Neužívejte dílo komerčně 4.0 International | cs |
dc.rights | Creative Commons Attribution-NonCommercial 4.0 International | en |
dc.title | DDI2 protease controls embryonic development and inflammation via TCF11/NRF1 | en |
dcterms.accessRights | openAccess | |
dcterms.license | https://creativecommons.org/licenses/by-nc/4.0/legalcode | |
dc.date.updated | 2025-02-13T14:11:21Z | |
dc.subject.keyword | DDI2 protease | en |
dc.subject.keyword | proteasome | en |
dc.subject.keyword | ubiquitin | en |
dc.subject.keyword | ubiquitin protease | en |
dc.subject.keyword | TCF11/NRF1 | en |
dc.subject.keyword | NFE2L1 | en |
dc.subject.keyword | knock-out | en |
dc.subject.keyword | interferon | en |
dc.subject.keyword | bZIP transcription factor | en |
dc.subject.keyword | tank-binding kinase-1 | en |
dc.identifier.eissn | 2589-0042 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/MSM//PRIMUS/21/SCI/018 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/MSM//SVV260679 | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/GA0/GA/GA22-16389S | |
dc.relation.fundingReference | info:eu-repo/grantAgreement/UK/COOP/COOP | |
dc.date.embargoStartDate | 2025-02-13 | |
dc.type.obd | 73 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | |
dc.identifier.doi | 10.1016/j.isci.2024.110893 | |
dc.identifier.utWos | 001318582000001 | |
dc.identifier.eidScopus | 2-s2.0-85207346406 | |
dc.identifier.obd | 652436 | |
dc.identifier.pubmed | 39328932 | |
dc.subject.rivPrimary | 10000::10600 | |
dcterms.isPartOf.name | iScience | |
dcterms.isPartOf.issn | 2589-0042 | |
dcterms.isPartOf.journalYear | 2024 | |
dcterms.isPartOf.journalVolume | 27 | |
dcterms.isPartOf.journalIssue | 10 | |
uk.faculty.primaryId | 108 | |
uk.faculty.primaryName | 1. lékařská fakulta | cs |
uk.faculty.primaryName | First Faculty of Medicine | en |
uk.faculty.secondaryId | 115 | |
uk.faculty.secondaryName | Přírodovědecká fakulta | cs |
uk.faculty.secondaryName | Faculty of Science | en |
uk.department.primaryId | 108 | |
uk.department.primaryName | 1. lékařská fakulta | cs |
uk.department.primaryName | First Faculty of Medicine | en |
uk.department.secondaryId | 1492 | |
uk.department.secondaryId | 1034 | |
uk.department.secondaryName | Ústav biochemie a experimentální onkologie 1. LF UK | cs |
uk.department.secondaryName | Institute of Biochemistry and Experimental Oncology | en |
uk.department.secondaryName | Katedra genetiky a mikrobiologie | cs |
uk.department.secondaryName | Department of Genetics and Microbiology | en |
dc.type.obdHierarchyCs | ČLÁNEK V ČASOPISU::článek v časopisu::původní článek | cs |
dc.type.obdHierarchyEn | JOURNAL ARTICLE::journal article::original article | en |
dc.type.obdHierarchyCode | 73::152::206 | en |
uk.displayTitle | DDI2 protease controls embryonic development and inflammation via TCF11/NRF1 | en |