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J. Biol. Chem., Vol. 280, Issue 14, 13973-13977, April 8, 2005
Mitosin/CENP-F as a Negative Regulator of Activating Transcription Factor-4*![]() ![]() ![]() ![]() ¶![]() ![]() ![]() ![]() ![]() ![]() ||
From the
Mitosin/CENP-F is a human nuclear matrix protein with multiple leucine zipper motifs. Its accumulation in S-G2 phases and transient kinetochore localization in mitosis suggest a multifunctional protein for cell proliferation. Moreover, its murine and avian orthologs are implicated in myocyte differentiation. Here we report its interaction with activating transcription factor-4 (ATF4), a ubiquitous basic leucine zipper transcription factor important for proliferation, differentiation, and stress response. The C-terminal portion of mitosin between residues 2488 and 3113 bound to ATF4 through two distinct domains, one of which was a leucine zipper motif. Mitosin mutants containing these domains were able to either supershift or disrupt the ATF4-DNA complex. On the other hand, ATF4, but not ATF13 or ATF6, interacted with mitosin through a region containing the basic leucine zipper motif. Moreover, overexpression of full-length mitosin repressed the transactivation activity of ATF4 in dual luciferase-based reporter assays, while knocking down mitosin expression manifested the opposite effects. These findings suggest mitosin to be a negative regulator of ATF4 in interphase through direct interaction.
Received for publication, December 20, 2004 , and in revised form, January 24, 2005. * This work was supported by Grants 30025021, 30330330, and 30421005 from the Natural Science Foundation of China. 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.
|| To whom correspondence should be addressed: Institute of Biochemistry and Cell Biology, 320 Yue Yang Rd., Shanghai 200031, China. Tel.: 86-21-54921406; Fax: 86-21-54921011; E-mail: xlzhu{at}sibs.ac.cn.
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