Discovery of USP53 and USP54 deubiquitinase activities

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dc.contributor.advisorGersch, Malte
dc.contributor.authorWendrich, Kim Solveig
dc.contributor.refereeWaldmann, Herbert
dc.date.accepted2025-06-16
dc.date.accessioned2025-07-16T05:46:16Z
dc.date.available2025-07-16T05:46:16Z
dc.date.issued2025
dc.description.abstractDeubiquitinating enzymes (DUBs) are proteases that cleave isopeptide bonds in between ubiquitin chains or between ubiquitin and substrates. Thereby, they determine the final ubiquitination status of substrates regulating their activity, localization, stability or cellular function. USP53 and USP54 are classified as DUBs but have previously been reported to be catalytically inactive. Both have been associated with cancer, and USP53 with cholestasis and hearing loss. However, a molecular understanding of their activities, functions, and disease association remains elusive. In this study, the catalytic activity of USP53 and USP54 was investigated by expression and purification of the catalytic domains, followed by biochemical and structural characterization. The results of this study establish USP53 and USP54 as active DUBs with distinct molecular mechanisms for the length-dependent decoding of K63-linked ubiquitin chains and will guide the analysis of their cellular functions. In addition, loss of USP53 activity was identified as a likely cause of the observed cholestasis phenotype, highlighting the importance of the catalytic activity of DUBs in the context of disease.en
dc.identifier.urihttp://hdl.handle.net/2003/43804
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-25578
dc.language.isoen
dc.subjectDeubiquitinaseen
dc.subjectDUBen
dc.subjectUSP53en
dc.subjectUSP54en
dc.subjectActivityen
dc.subjectCrystallographyen
dc.subject.ddc570
dc.subject.ddc540
dc.subject.rswkProteasende
dc.subject.rswkUbiquitinde
dc.titleDiscovery of USP53 and USP54 deubiquitinase activitiesen
dc.typeText
dc.type.publicationtypePhDThesis
dcterms.accessRightsopen access
eldorado.secondarypublicationfalse

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