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U.S.A."],"published-print":{"date-parts":[[2017,5,30]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The ATPase p97 plays an important cellular role by extracting proteins modified with ubiquitin (Ub) from membranes, chromatin, or protein complexes. However, the unstable and complicated nature of p97 substrates has hindered a detailed study of mechanism. To overcome these issues, we developed Ub-GFP as a fluorescent reporter of p97 activity. When Ub-GFP is conjugated with ubiquitin chains, p97 and its cofactor NPLOC4-UFD1L unfold it in an ATP-dependent manner, explicitly demonstrating that p97 is an unfoldase. We also show that a p97 mutation associated with multisystem proteinopathy has enhanced unfoldase activity, which suggests a novel approach to disease therapy. 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