Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase.
Abstract
Degradation of specific protein substrates by the anaphase-promoting complex/cyclosome
(APC) is critical for mitotic exit. We have identified the protein Xenopus nuclear
factor 7 (Xnf7) as a novel APC inhibitor able to regulate the timing of exit from
mitosis. Immunodepletion of Xnf7 from Xenopus laevis egg extracts accelerated the
degradation of APC substrates cyclin B1, cyclin B2, and securin upon release from
cytostatic factor arrest, whereas excess Xnf7 inhibited APC activity. Interestingly,
Xnf7 exhibited intrinsic ubiquitin ligase activity, and this activity was required
for APC inhibition. Unlike other reported APC inhibitors, Xnf7 did not associate with
Cdc20, but rather bound directly to core subunits of the APC. Furthermore, Xnf7 was
required for spindle assembly checkpoint function in egg extracts. These data suggest
that Xnf7 is an APC inhibitor able to link spindle status to the APC through direct
association with APC core components.
Type
Journal articleSubject
Anaphase-Promoting Complex-CyclosomeAnimals
Cyclin B
Cyclin B1
Female
Mitosis
Nuclear Proteins
Oocytes
Phosphoproteins
Protein Binding
Recombinant Proteins
Spindle Apparatus
Ubiquitin-Protein Ligase Complexes
Xenopus
Xenopus Proteins
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https://hdl.handle.net/10161/8379Published Version (Please cite this version)
10.1083/jcb.200411056Publication Info
Casaletto, Jessica B; Nutt, Leta K; Wu, Qiju; Moore, Jonathan D; Etkin, Laurence D;
Jackson, Peter K; ... Kornbluth, Sally (2005). Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase. J Cell Biol, 169(1). pp. 61-71. 10.1083/jcb.200411056. Retrieved from https://hdl.handle.net/10161/8379.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Sally A. Kornbluth
Jo Rae Wright University Distinguished Professor Emerita
Our lab studies the regulation of complex cellular processes, including cell cycle
progression and programmed cell death (apoptosis). These tightly orchestrated processes
are critical for appropriate cell proliferation and cell death, and when they go awry
can result in cancer and degenerative disorders. Within these larger fields, we have
focused on understanding the cellular mechanisms that prevent the onset of mitosis
prior to the completion of DNA replication, the process

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