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J. Biol. Chem., Vol. 281, Issue 37, 27426-27435, September 15, 2006

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The Transcriptional Activity of CITED1 Is Regulated by Phosphorylation in a Cell Cycle-dependent Manner^*

Genbin Shi, Scott C. Boyle, Duncan B. Sparrow¹, Sally L. Dunwoodie², Toshi Shioda^¶, and Mark P. de Caestecker³

From the Departments of Medicine, Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2372, the ^¶Department of Tumor Biology, Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts 02129, and the Victor Chang Cardiac Research Institute, University of New South Wales, Sydney, NSW 2010, Australia

CITED1 is the founding member of the CITED family of cofactors that are involved in regulating a wide variety of CBP/p300-dependent transcriptional responses. In the present study, we show that the phosphorylation status of CITED1 changes during the cell cycle and affects its transcriptional cofactor activity. Tryptic mapping and mutagenesis studies identified five phosphorylated serine residues in CITED1. Phosphorylation of these residues did not affect CRM1-dependent nuclear export, but did decrease CITED1 binding to p300 and inhibited CITED1-dependent transactivation of Smad4 and p300. These results suggest that CITED1 functions as a cell cycle-dependent transcriptional cofactor whose activity is regulated by phosphorylation.

Received for publication, March 21, 2006 , and in revised form, July 21, 2006.

This paper is dedicated to the memory of Anita Roberts (March 4, 1942-May 26, 2006).

^* This work was supported in part by National Institutes of Health Grant R01DK61558 and National Health and Medical Research Council Project Grant 303705. 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 Westfield Belconnen Postdoctoral Fellow.

² Pfizer Foundation of Australia Senior Research Fellow.

³ To whom correspondence should be addressed: Division of Nephrology, Vanderbilt University Medical Center, S-3223, Medical Center North, 1161 21st St. S, Nashville, TN 37232-2372. Tel.: 615-343-2844; Fax: 615-343-2675; E-mail: Mark.de.Caestecker{at}vanderbilt.edu.

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