Matches in SemOpenAlex for { <https://semopenalex.org/work/W3111148430> ?p ?o ?g. }
- W3111148430 abstract "SUMMARY DDI2 is an aspartic protease that cleaves polyubiquitinated substrates. Upon proteotoxic stress, DDI2 activates the ER-bound transcription factor TCF11/NRF1 (NFE2L1), a master regulator of proteostasis maintenance in mammalian cells, and ensures the expression of rescue factors including proteasome subunits. Here we describe the consequences of DDI2 ablation both in vivo and in cells. Knock-out of DDI2 in mice resulted in embryonic lethality at E12.5 with severe developmental failure. Molecular characterization of the embryos and surrogate DDI2 knock-out cell lines showed insufficient proteasome expression with proteotoxic stress, accumulation of high molecular weight ubiquitin conjugates, and induction of the unfolded protein and integrated stress responses. We also show that DDI2 KO-induced proteotoxic stress causes the cell-autonomous innate immune system to induce a type I interferon signature. These results indicate an important role for DDI2 in the proteostasis network of cells and tissues and in the maintenance of a balanced immune response. Highlights DDI2-deficiency in mice causes severe developmental failure and embryonic lethality at mid-late gestation DDI2-deficiency causes severe proteotoxic stress and proteasome impairment DDI2-deficiency induces the UPR and ISR signaling pathways DDI2-deficient cells survive via STAT3-dependent interferon signaling" @default.
- W3111148430 created "2020-12-21" @default.
- W3111148430 creator A5003007213 @default.
- W3111148430 creator A5004407181 @default.
- W3111148430 creator A5015541798 @default.
- W3111148430 creator A5032094873 @default.
- W3111148430 creator A5047486697 @default.
- W3111148430 creator A5057324531 @default.
- W3111148430 creator A5060922934 @default.
- W3111148430 creator A5063958049 @default.
- W3111148430 creator A5067537097 @default.
- W3111148430 creator A5073798958 @default.
- W3111148430 creator A5081388753 @default.
- W3111148430 date "2020-12-16" @default.
- W3111148430 modified "2023-10-16" @default.
- W3111148430 title "DDI2 protease activity controls embryonic development and inflammation via TCF11/NRF1" @default.
- W3111148430 cites W1031864925 @default.
- W3111148430 cites W1542932778 @default.
- W3111148430 cites W1789511037 @default.
- W3111148430 cites W1874540290 @default.
- W3111148430 cites W1947552193 @default.
- W3111148430 cites W1964443702 @default.
- W3111148430 cites W1965754110 @default.
- W3111148430 cites W1987011447 @default.
- W3111148430 cites W1987239731 @default.
- W3111148430 cites W1987334631 @default.
- W3111148430 cites W1989541636 @default.
- W3111148430 cites W1991558827 @default.
- W3111148430 cites W2003755766 @default.
- W3111148430 cites W2016814206 @default.
- W3111148430 cites W2021598579 @default.
- W3111148430 cites W2033742399 @default.
- W3111148430 cites W2051641469 @default.
- W3111148430 cites W2053205870 @default.
- W3111148430 cites W2053593146 @default.
- W3111148430 cites W2054827827 @default.
- W3111148430 cites W2063363508 @default.
- W3111148430 cites W2065462549 @default.
- W3111148430 cites W2067391810 @default.
- W3111148430 cites W2067813647 @default.
- W3111148430 cites W2083439589 @default.
- W3111148430 cites W2084288679 @default.
- W3111148430 cites W2097164847 @default.
- W3111148430 cites W2101791034 @default.
- W3111148430 cites W2102379760 @default.
- W3111148430 cites W2102839649 @default.
- W3111148430 cites W2104039873 @default.
- W3111148430 cites W2128016314 @default.
- W3111148430 cites W2149136460 @default.
- W3111148430 cites W2159510917 @default.
- W3111148430 cites W2159659449 @default.
- W3111148430 cites W2160188479 @default.
- W3111148430 cites W2162695817 @default.
- W3111148430 cites W2174297860 @default.
- W3111148430 cites W2282624086 @default.
- W3111148430 cites W2340472985 @default.
- W3111148430 cites W2344704339 @default.
- W3111148430 cites W2430142688 @default.
- W3111148430 cites W2479217913 @default.
- W3111148430 cites W2483485727 @default.
- W3111148430 cites W2508901115 @default.
- W3111148430 cites W2517628321 @default.
- W3111148430 cites W2518959324 @default.
- W3111148430 cites W2521385000 @default.
- W3111148430 cites W2526995495 @default.
- W3111148430 cites W2533155350 @default.
- W3111148430 cites W2547803093 @default.
- W3111148430 cites W2551965620 @default.
- W3111148430 cites W2558339860 @default.
- W3111148430 cites W2560204043 @default.
- W3111148430 cites W2578574899 @default.
- W3111148430 cites W2589476559 @default.
- W3111148430 cites W2606738783 @default.
- W3111148430 cites W2610977937 @default.
- W3111148430 cites W2615829409 @default.
- W3111148430 cites W2751182982 @default.
- W3111148430 cites W2758367786 @default.
- W3111148430 cites W2768617862 @default.
- W3111148430 cites W2776494444 @default.
- W3111148430 cites W2779339038 @default.
- W3111148430 cites W2786283343 @default.
- W3111148430 cites W2791098185 @default.
- W3111148430 cites W2796690375 @default.
- W3111148430 cites W2888480058 @default.
- W3111148430 cites W2889289659 @default.
- W3111148430 cites W2892347994 @default.
- W3111148430 cites W2907034604 @default.
- W3111148430 cites W2907903894 @default.
- W3111148430 cites W2913940235 @default.
- W3111148430 cites W2922286507 @default.
- W3111148430 cites W2944395577 @default.
- W3111148430 cites W2948687075 @default.
- W3111148430 cites W2949347917 @default.
- W3111148430 cites W2954867976 @default.
- W3111148430 cites W2956030496 @default.
- W3111148430 cites W2968429984 @default.
- W3111148430 cites W2980804175 @default.
- W3111148430 cites W2983017086 @default.
- W3111148430 cites W2988684981 @default.
- W3111148430 cites W2991562434 @default.