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.
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11 April 2005
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April 11 2005
Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase
Jessica B. Casaletto,
Jessica B. Casaletto
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
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Leta K. Nutt,
Leta K. Nutt
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
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Qiju Wu,
Qiju Wu
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
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Jonathan D. Moore,
Jonathan D. Moore
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
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Laurence D. Etkin,
Laurence D. Etkin
2Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
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Peter K. Jackson,
Peter K. Jackson
3Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
4Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
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Tim Hunt,
Tim Hunt
5Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, England, UK
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Sally Kornbluth
Sally Kornbluth
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
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Jessica B. Casaletto
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
Leta K. Nutt
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
Qiju Wu
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
Jonathan D. Moore
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
Laurence D. Etkin
2Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
Peter K. Jackson
3Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305
4Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
Tim Hunt
5Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, England, UK
Sally Kornbluth
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710
Correspondence to S. Kornbluth: [email protected]
Abbreviations used in this paper: APC, anaphase-promoting complex/cyclosome; CRS, cytoplasmic retention sequence; CSF, cytostatic factor; IAP, inhibitor of apoptosis; RRL, rabbit reticulocyte lysate; Xnf7, Xenopus nuclear factor 7.
Received:
November 08 2004
Accepted:
March 07 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (1): 61–71.
Article history
Received:
November 08 2004
Accepted:
March 07 2005
Citation
Jessica B. Casaletto, Leta K. Nutt, Qiju Wu, Jonathan D. Moore, Laurence D. Etkin, Peter K. Jackson, Tim Hunt, Sally Kornbluth; Inhibition of the anaphase-promoting complex by the Xnf7 ubiquitin ligase . J Cell Biol 11 April 2005; 169 (1): 61–71. doi: https://doi.org/10.1083/jcb.200411056
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