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J. Biol. Chem., Vol. 281, Issue 43, 32284-32293, October 27, 2006
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3
From the
Howard Hughes Medical Institute and the Departments of
Cell and Developmental Biology and ¶Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
The anaphase-promoting complex/cyclosome (APC/C) is a conserved multisubunit ubiquitin ligase required for the degradation of key cell cycle regulators. The APC/C becomes active at the metaphase/anaphase transition and remains active during G1 phase. One mechanism linked to activation of the APC/C is phosphorylation. Although many sites of mitotic phosphorylation have been identified in core components of the APC/C, the consequence of any individual phosphorylation event has not been elucidated in vivo. In this study, we show that Hcn1 is an essential core component of the fission yeast APC/C and is critical for maintaining complex integrity. Moreover, Hcn1 is a phosphoprotein in vivo. Phosphorylation of Hcn1 occurs at a single Cdk1 site in vitro and in vivo. Mutation of this site to alanine, but not aspartic acid, compromises APC/C function and leads to a specific defect in the completion of cell division.
Received for publication, April 21, 2006 , and in revised form, August 31, 2006.
* This work was supported in part by National Institutes of Health Grant GM47728. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Supported by National Institutes of Health Grants GM64779 and HL68744.
2 Supported by National Institutes of Health Grants GM64779, HL68744, ES11993, and CA098131.
3 Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed. Tel.: 615-343-9502; Fax: 615-343-0723; E-mail: kathy.gould{at}vanderbilt.edu.
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