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@ARTICLE{vanWell:140707,
      author       = {van Well, Eva M and Bader, Verian and Patra, Maria and
                      Sánchez-Vicente, Ana and Meschede, Jens and Furthmann,
                      Nikolas and Schnack, Cathrin and Blusch, Alina and
                      Longworth, Joseph and Petrasch-Parwez, Elisabeth and Mori,
                      Kohji and Arzberger, Thomas and Trümbach, Dietrich and
                      Angersbach, Lena and Showkat, Cathrin and Sehr, Dominik A
                      and Berlemann, Lena A and Goldmann, Petra and Clement,
                      Albrecht M and Behl, Christian and Woerner, Andreas C and
                      Saft, Carsten and Wurst, Wolfgang and Haass, Christian and
                      Ellrichmann, Gisa and Gold, Ralf and Dittmar, Gunnar and
                      Hipp, Mark S and Hartl, F Ulrich and Tatzelt, Jörg and
                      Winklhofer, Konstanze F},
      title        = {{A} protein quality control pathway regulated by linear
                      ubiquitination.},
      journal      = {The EMBO journal},
      volume       = {38},
      number       = {9},
      issn         = {0261-4189},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2020-07029},
      pages        = {e100730},
      year         = {2019},
      abstract     = {Neurodegenerative diseases are characterized by the
                      accumulation of misfolded proteins in the brain. Insights
                      into protein quality control mechanisms to prevent neuronal
                      dysfunction and cell death are crucial in developing causal
                      therapies. Here, we report that various disease-associated
                      protein aggregates are modified by the linear ubiquitin
                      chain assembly complex (LUBAC). HOIP, the catalytic
                      component of LUBAC, is recruited to misfolded Huntingtin in
                      a p97/VCP-dependent manner, resulting in the assembly of
                      linear polyubiquitin. As a consequence, the interactive
                      surface of misfolded Huntingtin species is shielded from
                      unwanted interactions, for example with the low complexity
                      sequence domain-containing transcription factor Sp1, and
                      proteasomal degradation of misfolded Huntingtin is
                      facilitated. Notably, all three core LUBAC components are
                      transcriptionally regulated by Sp1, linking defective LUBAC
                      expression to Huntington's disease. In support of a
                      protective activity of linear ubiquitination, silencing of
                      OTULIN, a deubiquitinase with unique specificity for linear
                      polyubiquitin, decreases proteotoxicity, whereas silencing
                      of HOIP has the opposite effect. These findings identify
                      linear ubiquitination as a protein quality control mechanism
                      and hence a novel target for disease-modifying strategies in
                      proteinopathies.},
      keywords     = {Adult / Aged / Animals / Brain: metabolism / Brain:
                      pathology / Case-Control Studies / Cells, Cultured / Embryo,
                      Mammalian: cytology / Embryo, Mammalian: metabolism / Female
                      / Fibroblasts: cytology / Fibroblasts: metabolism / Humans /
                      Huntingtin Protein: genetics / Huntingtin Protein:
                      metabolism / Huntington Disease: genetics / Huntington
                      Disease: metabolism / Huntington Disease: pathology / Male /
                      Mice / Mice, Knockout / Middle Aged / NF-kappa B: genetics /
                      NF-kappa B: metabolism / Neurons: metabolism / Neurons:
                      pathology / Polyubiquitin: metabolism / Protein Binding /
                      Protein Interaction Domains and Motifs / Protein Processing,
                      Post-Translational / Signal Transduction / Sp1 Transcription
                      Factor: genetics / Sp1 Transcription Factor: metabolism /
                      Ubiquitination / Valosin Containing Protein: genetics /
                      Valosin Containing Protein: metabolism / HTT protein, human
                      (NLM Chemicals) / Huntingtin Protein (NLM Chemicals) /
                      NF-kappa B (NLM Chemicals) / Sp1 Transcription Factor (NLM
                      Chemicals) / Sp1 protein, human (NLM Chemicals) /
                      Polyubiquitin (NLM Chemicals) / Valosin Containing Protein
                      (NLM Chemicals)},
      cin          = {AG Levin / AG Wurst / AG Haass / AG Winklhofer},
      ddc          = {570},
      cid          = {I:(DE-2719)1111016 / I:(DE-2719)1140001 /
                      I:(DE-2719)1110007 / I:(DE-2719)5000047},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
                      - Clinical and Health Care Research (POF3-344) / 341 -
                      Molecular Signaling (POF3-341)},
      pid          = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344 /
                      G:(DE-HGF)POF3-341},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30886048},
      pmc          = {pmc:PMC6484417},
      doi          = {10.15252/embj.2018100730},
      url          = {https://pub.dzne.de/record/140707},
}