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Originally published In Press as doi:10.1074/jbc.M609924200 on November 10, 2006

J. Biol. Chem., Vol. 282, Issue 1, 168-175, January 5, 2007
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Mip/LIN-9 Regulates the Expression of B-Myb and the Induction of Cyclin A, Cyclin B, and CDK1*

Mark Pilkinton{ddagger}1, Raudel Sandoval{ddagger}, Julie Song{ddagger}, Scott A. Ness§, and Oscar R. Colamonici{ddagger}2

From the {ddagger}Department of Pharmacology, University of Illinois, Chicago, Illinois 60612 and the §Department of Molecular Genetics and Microbiology, University of New Mexico Health Science Center, Albuquerque, New Mexico 87131

Members of the novel family of proteins that include Drosophila Mip130, Caenorhabditis elegans LIN-9, and mammalian LIN-9 intervene in different cellular functions such as regulation of transcription, differentiation, transformation, and cell cycle progression. Here we demonstrate that LIN-9, designated as Mip/LIN-9, interacts with B-Myb but not with c-Myb or A-Myb. Mip/LIN-9 regulates the expression of B-Myb in a post-transcriptional manner, and its depletion not only decreases the level of the B-Myb protein but also affects the expression of S phase and mitotic genes (i.e. cyclin A, CDK1, and cyclin B). The critical role of Mip/LIN-9 on the expression of S and G2/M genes is further supported by the finding that coexpression of Mip/LIN-9 and B-Myb results in the activation of cyclin A and cyclin B promoter-luciferase reporters, and both proteins are detected on the cyclin A and B promoters. Interestingly, although Mip/LIN-9 promoter occupancy peaks earlier than B-Myb, the highest levels of expression of cyclins A and B correlate with the maximum binding of B-Myb to these promoters. These data support the concept that Mip/LIN-9 is required for the expression of B-Myb, and both proteins collaborate in the control of the cell cycle progression via the regulation of S phase and mitotic cyclins.


Received for publication, October 23, 2006

* This work was supported in part by National Institutes of Health Grant GM54709 (to O. R. C.). 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.

This paper is dedicated to our colleague Dr. Robert Costa who provided us with the cyclin B constructs and passed away before the completion of this work.

1 Supported by NRSA/NIDDK T32 Training Grant DK07739 from the National Institutes of Health.

2 To whom correspondence should be addressed: University of Illinois, Dept. of Pharmacology, 835 S. Wolcott, Rm. E403 (M/C 868), Chicago, IL 60612. Tel.: 312-413-4113; Fax: 312-413-4140 or 312-996-1225; E-mail: ocolamon{at}uic.edu.


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