title: 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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Jessica B
authors.initials: JB
authors.lastname: Casaletto
authors.forename: Leta K
authors.initials: LK
authors.lastname: Nutt
authors.forename: Qiju
authors.initials: Q
authors.lastname: Wu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Moore
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Etkin
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
authors.forename: Tim
authors.initials: T
authors.lastname: Hunt
authors.forename: Sally
authors.initials: S
authors.lastname: Kornbluth
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D004527:Egg Proteins; D005260:Female; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019926:Cyclin B; D056744:Cyclin B1; D004268:DNA-Binding Proteins; D004527:Egg Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D029867:Xenopus Proteins; C071551:XNF7 protein, Xenopus; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome