Hauptseite > Publikationsdatenbank > NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62 > print

001     1020576
005     20240610120202.0
024 7 _ |a 10.1038/s41467-023-44033-0
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100 1 _ |a Furthmann, Nikolas
|0 0000-0002-6643-7470
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245 _ _ |a NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62
260 _ _ |a [London]
|c 2023
|b Nature Publishing Group UK
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520 _ _ |a NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathwayactivation in innate immune signaling, cell death regulation and host-pathogeninteractions. Here we identify an NF-κB-independent function of NEMO inproteostasis regulation by promoting autophagosomal clearance of proteinaggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxicstress and are vulnerable to proteostasis challenges. Moreover, apatient with a mutation in the NEMO-encoding IKBKG gene resulting indefective binding of NEMO to linear ubiquitin chains, developed a widespreadmixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology.NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotesthe local concentration of p62 into foci. In vitro, NEMO lowers the thresholdconcentrations required for ubiquitin-dependent phase transition of p62. Insummary, NEMO reshapes the aggregate surface for efficient autophagosomalclearancebyprovidingamobilephase at theaggregate interphase favoringcocondensationwith p62.
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700 1 _ |a Blusch, Alina
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700 1 _ |a Goel, Simran
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700 1 _ |a Sánchez-Vicente, Ana
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700 1 _ |a Krause, Laura J.
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700 1 _ |a Chaban, Sarah A.
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700 1 _ |a Grover, Prerna
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700 1 _ |a Trinkaus, Victoria A.
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700 1 _ |a van Well, Eva M.
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700 1 _ |a Jaugstetter, Maximilian
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700 1 _ |a Tschulik, Kristina
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700 1 _ |a Damgaard, Rune Busk
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700 1 _ |a Saft, Carsten
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700 1 _ |a Ellrichmann, Gisa
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700 1 _ |a Gold, Ralf
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700 1 _ |a Koch, Arend
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700 1 _ |a Englert, Benjamin
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700 1 _ |a Westenberger, Ana
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700 1 _ |a Klein, Christine
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700 1 _ |a Jungbluth, Lisa
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700 1 _ |a Sachse, Carsten
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700 1 _ |a Behrends, Christian
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700 1 _ |a Glatzel, Markus
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700 1 _ |a Hartl, F. Ulrich
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700 1 _ |a Nakamura, Ken
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700 1 _ |a Christine, Chadwick W.
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700 1 _ |a Huang, Eric J.
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700 1 _ |a Tatzelt, Jörg
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700 1 _ |a Winklhofer, Konstanze F.
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773 _ _ |a 10.1038/s41467-023-44033-0
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