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| 001 | 299495 | ||
| 005 | 20250401142320.0 | ||
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| 024 | 7 | _ | |a 0261-4189 |2 ISSN |
| 024 | 7 | _ | |a 1460-2075 |2 ISSN |
| 024 | 7 | _ | |a DOI:10.1038/s44318-025-00381-9 |2 doi |
| 024 | 7 | _ | |a DOI:10.1038/s44318-025-00381-9 |2 doi |
| 024 | 7 | _ | |a altmetric:174568898 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2025-00454 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Škapik, Ivana Paskov |b 0 |
| 245 | _ | _ | |a Maintenance of p-eIF2α levels by the eIF2B complex is vital for colorectal cancer. |
| 260 | _ | _ | |a [London] |c 2025 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1743510157_5886 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a ZMBH Alliance / EMBO J, (2025), 44: 2075 - 2105 |
| 520 | _ | _ | |a Protein synthesis is an essential process, deregulated in multiple tumor types showing differential dependence on translation factors compared to untransformed tissue. We show that colorectal cancer (CRC) with loss-of-function mutation in the APC tumor suppressor depends on an oncogenic translation program regulated by the ability to sense phosphorylated eIF2α (p-eIF2α). Despite increased protein synthesis rates following APC loss, eIF2α phosphorylation, typically associated with translation inhibition, is enhanced in CRC. Elevated p-eIF2α, and its proper sensing by the decameric eIF2B complex, are essential to balance translation. Knockdown or mutation of eIF2Bα and eIF2Bδ, two eIF2B subunits responsible for sensing p-eIF2α, impairs CRC viability, demonstrating that the eIF2B/p-eIF2α nexus is vital for CRC. Specifically, the decameric eIF2B linked by two eIF2Bα subunits is critical for translating growth-promoting mRNAs which are induced upon APC loss. Depletion of eIF2Bα in APC-deficient murine and patient-derived organoids establishes a therapeutic window, validating eIF2Bα as a target for clinical intervention. In conclusion, we demonstrate how the expression of the oncogenic signature in CRC is crucially controlled at the translational level. |
| 536 | _ | _ | |a 311 - Zellbiologie und Tumorbiologie (POF4-311) |0 G:(DE-HGF)POF4-311 |c POF4-311 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to DataCite, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a APC |2 Other |
| 650 | _ | 7 | |a Colorectal Cancer |2 Other |
| 650 | _ | 7 | |a Translation |2 Other |
| 650 | _ | 7 | |a eIF2B |2 Other |
| 650 | _ | 7 | |a eIF2α |2 Other |
| 700 | 1 | _ | |a Giacomelli, Chiara |b 1 |
| 700 | 1 | _ | |a Hahn, Sarah |b 2 |
| 700 | 1 | _ | |a Deinlein, Hanna |b 3 |
| 700 | 1 | _ | |a Gallant, Peter |0 0000-0002-8270-5738 |b 4 |
| 700 | 1 | _ | |a Diebold, Mathias |0 0000-0002-7595-3901 |b 5 |
| 700 | 1 | _ | |a Biayna, Josep |0 0000-0002-0842-7530 |b 6 |
| 700 | 1 | _ | |a Hendricks, Anne |b 7 |
| 700 | 1 | _ | |a Olimski, Leon |b 8 |
| 700 | 1 | _ | |a Otto, Christoph |b 9 |
| 700 | 1 | _ | |a Kastner, Carolin |b 10 |
| 700 | 1 | _ | |a Wolf, Elmar |b 11 |
| 700 | 1 | _ | |a Schülein-Völk, Christina |b 12 |
| 700 | 1 | _ | |a Maurus, Katja |b 13 |
| 700 | 1 | _ | |a Rosenwald, Andreas |b 14 |
| 700 | 1 | _ | |a Schleussner, Nikolai |0 P:(DE-HGF)0 |b 15 |
| 700 | 1 | _ | |a Jackstadt, Rene-Filip |0 P:(DE-He78)5da14633266cbfff7746cf529c110673 |b 16 |u dkfz |
| 700 | 1 | _ | |a Schlegel, Nicolas |b 17 |
| 700 | 1 | _ | |a Germer, Christoph-Thomas |b 18 |
| 700 | 1 | _ | |a Bushell, Martin |b 19 |
| 700 | 1 | _ | |a Eilers, Martin |0 0000-0002-0376-6533 |b 20 |
| 700 | 1 | _ | |a Schmidt, Stefanie |0 0000-0003-2053-0909 |b 21 |
| 700 | 1 | _ | |a Wiegering, Armin |0 0000-0001-7777-0909 |b 22 |
| 773 | _ | _ | |a DOI:10.1038/s44318-025-00381-9 |0 PERI:(DE-600)1467419-1 |p 2075 - 2105 |t The EMBO journal |v 44 |y 2025 |x 0261-4189 |
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