دورية أكاديمية
A protein quality control pathway regulated by linear ubiquitination
| العنوان: | A protein quality control pathway regulated by linear ubiquitination |
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| المؤلفون: | Well, Eva M. van, Bader, Verian, Patra, Maria, Sanchez-Vicente, Ana, Meschede, Jens, Furthmann, Nikolas, Schnack, Cathrin, Blusch, Alina, Longworth, Joseph, Petrasch-Parwez, Elisabeth, Mori, Kohji, Arzberger, Thomas, Truembach, Dietrich, Angersbach, Lena, Showkat, Cathrin, Sehr, Dominik A., Berlemann, Lena A., Goldmann, Petra, Clement, Albrecht M., Behl, Christian, Woerner, Andreas C., Saft, Carsten, Wurst, Wolfgang, Haass, Christian, Ellrichmann, Gisa, Gold, Ralf, Dittmar, Gunnar, Hipp, Mark S., Hartl, F. Ulrich, Tatzelt, Jörg, Winklhofer, Konstanze F. |
| المصدر: | EMBO Journal |
| بيانات النشر: | Ludwig-Maximilians-Universität München |
| سنة النشر: | 2019 |
| المجموعة: | Open Access LMU (Ludwig-Maximilians-University Munich) |
| مصطلحات موضوعية: | Medizin, Munich Cluster for Systems Neurology (SyNergy), ddc:610 |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | Well, Eva M. van; Bader, Verian; Patra, Maria; Sanchez-Vicente, Ana; Meschede, Jens; Furthmann, Nikolas; Schnack, Cathrin; Blusch, Alina; Longworth, Joseph; Petrasch-Parwez, Elisabeth; Mori, Kohji; Arzberger, Thomas; Truembach, Dietrich; Angersbach, Lena; Showkat, Cathrin; Sehr, Dominik A.; Berlemann, Lena A.; Goldmann, Petra; Clement, Albrecht M.; Behl, Christian; Woerner, Andreas C.; Saft, Carsten; Wurst, Wolfgang; Haass, Christian; Ellrichmann, Gisa; Gold, Ralf; Dittmar, Gunnar; Hipp, Mark S.; Hartl, F. Ulrich; Tatzelt, Jörg und Winklhofer, Konstanze F. (2019): A protein quality control pathway regulated by linear ubiquitination. In: EMBO Journal, Bd. 38, Nr. 9, e100730 [PDF, 2MB]; https://epub.ub.uni-muenchen.de/79972/1/van-well-et-al-2019-a-protein-quality-control-pathway-regulated-by-linear-ubiquitination.pdfTest; http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-79972-2Test; https://epub.ub.uni-muenchen.de/79972Test/ |
| DOI: | 10.15252/embj.2018100730 |
| الإتاحة: | https://doi.org/10.15252/embj.2018100730Test https://epub.ub.uni-muenchen.de/79972/1/van-well-et-al-2019-a-protein-quality-control-pathway-regulated-by-linear-ubiquitination.pdfTest https://epub.ub.uni-muenchen.de/79972Test/ http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-79972-2Test |
| رقم الانضمام: | edsbas.4B2E24EE |
| قاعدة البيانات: | BASE |
| DOI: | 10.15252/embj.2018100730 |
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