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@ARTICLE{Lammich:136395,
      author       = {Lammich, Sven and Kamp, Frits and Wagner, Judith and
                      Nuscher, Brigitte and Zilow, Sonja and Ludwig, Ann-Katrin
                      and Willem, Michael and Haass, Christian},
      title        = {{T}ranslational repression of the disintegrin and
                      metalloprotease {ADAM}10 by a stable {G}-quadruplex
                      secondary structure in its 5'-untranslated region.},
      journal      = {The journal of biological chemistry},
      volume       = {286},
      number       = {52},
      issn         = {0021-9258},
      address      = {Bethesda, Md.},
      publisher    = {Soc.60645},
      reportid     = {DZNE-2020-02717},
      pages        = {45063-45072},
      year         = {2011},
      abstract     = {Anti-amyloidogenic processing of the amyloid precursor
                      protein APP by α-secretase prevents formation of the
                      amyloid-β peptide, which accumulates in senile plaques of
                      Alzheimer disease patients. α-Secretase belongs to the
                      family of a disintegrin and metalloproteases (ADAMs), and
                      ADAM10 is the primary candidate for this anti-amyloidogenic
                      activity. We recently demonstrated that ADAM10 translation
                      is repressed by its 5'-UTR and that in particular the first
                      half of ADAM10 5'-UTR is responsible for translational
                      repression. Here, we asked whether specific sequence motifs
                      exist in the ADAM10 5'-UTR that are able to form complex
                      secondary structures and thus potentially inhibit ADAM10
                      translation. Using circular dichroism spectroscopy, we
                      demonstrate that a G-rich region between nucleotides 66 and
                      94 of the ADAM10 5'-UTR forms a highly stable,
                      intramolecular, parallel G-quadruplex secondary structure
                      under physiological conditions. Mutation of guanines in this
                      sequence abrogates the formation of the G-quadruplex
                      structure. Although the G-quadruplex structure efficiently
                      inhibits translation of a luciferase reporter in in vitro
                      translation assays and in living cells, inhibition of
                      G-quadruplex formation fails to do so. Moreover, expression
                      of ADAM10 was similarly repressed by the G-quadruplex.
                      Mutation of the G-quadruplex motif results in a significant
                      increase of ADAM10 levels and consequently APPsα secretion.
                      Thus, we identified a critical RNA secondary structure
                      within the 5'-UTR, which contributes to the translational
                      repression of ADAM10.},
      keywords     = {5' Untranslated Regions: physiology / ADAM Proteins:
                      biosynthesis / ADAM Proteins: genetics / ADAM10 Protein /
                      Amyloid Precursor Protein Secretases: biosynthesis / Amyloid
                      Precursor Protein Secretases: genetics / HEK293 Cells /
                      Humans / Membrane Proteins: biosynthesis / Membrane
                      Proteins: genetics / Mutation / Nucleic Acid Conformation /
                      Protein Biosynthesis: physiology / 5' Untranslated Regions
                      (NLM Chemicals) / Membrane Proteins (NLM Chemicals) /
                      Amyloid Precursor Protein Secretases (NLM Chemicals) / ADAM
                      Proteins (NLM Chemicals) / ADAM10 Protein (NLM Chemicals) /
                      ADAM10 protein, human (NLM Chemicals)},
      cin          = {AG Haass old},
      ddc          = {540},
      cid          = {I:(DE-2719)1110007},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:22065584},
      pmc          = {pmc:PMC3248004},
      doi          = {10.1074/jbc.M111.296921},
      url          = {https://pub.dzne.de/record/136395},
}