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Cezanne/ OTUD 7B is a cell cycle‐regulated deubiquitinase that antagonizes the degradation of APC /C substrates
Author(s) -
Bonacci Thomas,
Suzuki Aussie,
Grant Gavin D,
Stanley Natalie,
Cook Jeanette G,
Brown Nicholas G,
Emanuele Michael J
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798701
Subject(s) - chapel , art , art history
The anaphase‐promoting complex/cyclosome ( APC /C) is an E3 ubiquitin ligase and key regulator of cell cycle progression. Since APC /C promotes the degradation of mitotic cyclins, it controls cell cycle‐dependent oscillations in cyclin‐dependent kinase ( CDK ) activity. Both CDK s and APC /C control a large number of substrates and are regulated by analogous mechanisms, including cofactor‐dependent activation. However, whereas substrate dephosphorylation is known to counteract CDK , it remains largely unknown whether deubiquitinating enzymes ( DUB s) antagonize APC /C substrate ubiquitination during mitosis. Here, we demonstrate that Cezanne/ OTUD 7B is a cell cycle‐regulated DUB that opposes the ubiquitination of APC /C targets. Cezanne is remarkably specific for K11‐linked ubiquitin chains, which are formed by APC /C in mitosis. Accordingly, Cezanne binds established APC /C substrates and reverses their APC /C‐mediated ubiquitination. Cezanne depletion accelerates APC /C substrate degradation and causes errors in mitotic progression and formation of micronuclei. These data highlight the importance of tempered APC /C substrate destruction in maintaining chromosome stability. Furthermore, Cezanne is recurrently amplified and overexpressed in numerous malignancies, suggesting a potential role in genome maintenance and cancer cell proliferation.