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@ARTICLE{kapik:299495,
      author       = {I. P. Škapik and C. Giacomelli and S. Hahn and H. Deinlein
                      and P. Gallant and M. Diebold and J. Biayna and A. Hendricks
                      and L. Olimski and C. Otto and C. Kastner and E. Wolf and C.
                      Schülein-Völk and K. Maurus and A. Rosenwald and N.
                      Schleussner$^*$ and R.-F. Jackstadt$^*$ and N. Schlegel and
                      C.-T. Germer and M. Bushell and M. Eilers and S. Schmidt and
                      A. Wiegering},
      title        = {{M}aintenance of p-e{IF}2α levels by the e{IF}2{B} complex
                      is vital for colorectal cancer.},
      journal      = {The EMBO journal},
      volume       = {44},
      issn         = {0261-4189},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2025-00454},
      pages        = {2075 - 2105},
      year         = {2025},
      note         = {ZMBH Alliance / EMBO J, (2025), 44: 2075 - 2105},
      abstract     = {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.},
      keywords     = {APC (Other) / Colorectal Cancer (Other) / Translation
                      (Other) / eIF2B (Other) / eIF2α (Other)},
      cin          = {A013 / HD01},
      ddc          = {570},
      cid          = {I:(DE-He78)A013-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40016419},
      doi          = {DOI:10.1038/s44318-025-00381-9},
      url          = {https://inrepo02.dkfz.de/record/299495},
}