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Article

The Cdc48 Complex Alleviates the Cytotoxicity of Misfolded Proteins by Regulating Ubiquitin Homeostasis.

Cell reports - 14 Jul 2020

Higgins Ryan, Kabbaj Marie-Helene, Sherwin Delaney, Howell Lauren A, Hatcher Alexa, Tomko Robert J, Wang Yanchang

Abstract excerpt

The accumulation of misfolded proteins is associated with multiple neurodegenerative disorders, but it remains poorly defined how this accumulation causes cytotoxicity. Here, we demonstrate that the Cdc48/p97 segregase machinery drives the clearance of ubiquitinated model misfolded protein Huntingtin (Htt103QP) and limits its aggregation. Nuclear ubiquitin ligase San1 acts upstream of Cdc48 to ubiquitinate...

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Identifiers

PMID: 32668237
DOI: 10.1016/j.celrep.2020.107898
PMCID: PMC7392062

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