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001020576 1001_ $$00000-0002-6643-7470$$aFurthmann, Nikolas$$b0
001020576 245__ $$aNEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62
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001020576 520__ $$aNEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathwayactivation in innate immune signaling, cell death regulation and host-pathogeninteractions. Here we identify an NF-κB-independent function of NEMO inproteostasis regulation by promoting autophagosomal clearance of proteinaggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxicstress and are vulnerable to proteostasis challenges. Moreover, apatient with a mutation in the NEMO-encoding IKBKG gene resulting indefective binding of NEMO to linear ubiquitin chains, developed a widespreadmixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology.NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotesthe local concentration of p62 into foci. In vitro, NEMO lowers the thresholdconcentrations required for ubiquitin-dependent phase transition of p62. Insummary, NEMO reshapes the aggregate surface for efficient autophagosomalclearancebyprovidingamobilephase at theaggregate interphase favoringcocondensationwith p62.
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001020576 7001_ $$aBlusch, Alina$$b3
001020576 7001_ $$aGoel, Simran$$b4
001020576 7001_ $$aSánchez-Vicente, Ana$$b5
001020576 7001_ $$00000-0002-2086-3757$$aKrause, Laura J.$$b6
001020576 7001_ $$00009-0000-1543-4512$$aChaban, Sarah A.$$b7
001020576 7001_ $$00000-0001-5132-0635$$aGrover, Prerna$$b8
001020576 7001_ $$aTrinkaus, Victoria A.$$b9
001020576 7001_ $$avan Well, Eva M.$$b10
001020576 7001_ $$aJaugstetter, Maximilian$$b11
001020576 7001_ $$00000-0001-7637-4082$$aTschulik, Kristina$$b12
001020576 7001_ $$00000-0002-1709-6534$$aDamgaard, Rune Busk$$b13
001020576 7001_ $$aSaft, Carsten$$b14
001020576 7001_ $$aEllrichmann, Gisa$$b15
001020576 7001_ $$aGold, Ralf$$b16
001020576 7001_ $$aKoch, Arend$$b17
001020576 7001_ $$00000-0002-1769-5393$$aEnglert, Benjamin$$b18
001020576 7001_ $$aWestenberger, Ana$$b19
001020576 7001_ $$aKlein, Christine$$b20
001020576 7001_ $$0P:(DE-Juel1)177977$$aJungbluth, Lisa$$b21
001020576 7001_ $$0P:(DE-Juel1)173949$$aSachse, Carsten$$b22
001020576 7001_ $$00000-0002-9184-7607$$aBehrends, Christian$$b23
001020576 7001_ $$00000-0002-7720-8817$$aGlatzel, Markus$$b24
001020576 7001_ $$00000-0002-7941-135X$$aHartl, F. Ulrich$$b25
001020576 7001_ $$aNakamura, Ken$$b26
001020576 7001_ $$00000-0003-4166-9432$$aChristine, Chadwick W.$$b27
001020576 7001_ $$00000-0002-5381-3801$$aHuang, Eric J.$$b28
001020576 7001_ $$aTatzelt, Jörg$$b29
001020576 7001_ $$00000-0002-7256-8231$$aWinklhofer, Konstanze F.$$b30$$eCorresponding author
001020576 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-023-44033-0$$gVol. 14, no. 1, p. 8368$$n1$$p8368$$tNature Communications$$v14$$x2041-1723$$y2023
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