DDI2 protease controls embryonic development and inflammation via TCF11/NRF1
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00598945" target="_blank" >RIV/61388963:_____/24:00598945 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/24:00598945 RIV/00216208:11310/24:10484773 RIV/00216208:11110/24:10484773
Result on the web
<a href="https://doi.org/10.1016/j.isci.2024.110893" target="_blank" >https://doi.org/10.1016/j.isci.2024.110893</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.isci.2024.110893" target="_blank" >10.1016/j.isci.2024.110893</a>
Alternative languages
Result language
angličtina
Original language name
DDI2 protease controls embryonic development and inflammation via TCF11/NRF1
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
iScience
ISSN
2589-0042
e-ISSN
2589-0042
Volume of the periodical
27
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
26
Pages from-to
110893
UT code for WoS article
001318582000001
EID of the result in the Scopus database
2-s2.0-85207346406