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J. Biol. Chem., Vol. 283, Issue 17, 11135-11145, April 25, 2008
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From the Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84112
Previous studies have revealed many parallels in the cell cycle regulation of the Ace2 and Swi5 transcription factors. Although both proteins begin entry into the nucleus near the start of mitosis, here we show that Ace2 accumulates in the nucleus and binds DNA about 10 min later in the cell cycle than Swi5. We used chimeric fusions to identify the N-terminal region of Ace2 as responsible for the delay, and this same region of Ace2 was required for interaction with Cbk1, a kinase necessary for both transcriptional activation by Ace2 and asymmetric distribution of Ace2. Ace2 and Swi5 also showed differences in prevalence during the cell cycle. Swi5 is apparently degraded soon after nuclear entry, whereas constant Ace2 levels throughout the cell cycle suggest Ace2 is exported from the nucleus. Our work suggests that the precise timing of Ace2 accumulation in the nucleus involves both a nuclear export sequence and a nuclear localization signal, whose activities are regulated by phosphorylation.
Received for publication, January 9, 2008 , and in revised form, February 7, 2008.
* This work was supported in part by a grant from the National Institutes of Health (to D. J. S.). 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.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables 1–4.
1 Both authors contributed equally to this work.
2 Present address: Dept. of Oncological Sciences, University of Utah, Salt Lake City, UT 84112.
3 Supported by National Institutes of Health Training Grant T32-DK007115.
4 To whom correspondence should be addressed: Dept. of Pathology, University of Utah, 15 N. Medical Dr. East, Salt Lake City, UT 84112. Tel.: 801-581-5429; Fax: 801-581-4517; E-mail: david.stillman{at}utah.edu.
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