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J. Biol. Chem., Vol. 282, Issue 10, 6917-6921, March 9, 2007

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Prokineticin 2 Is a Target Gene of Proneural Basic Helix-Loop-Helix Factors for Olfactory Bulb Neurogenesis^*

Chengkang Zhang, Kwan L. Ng¹, Jia-Da Li, Fei He, David J. Anderson^¶, Yi E. Sun, and Qun-Yong Zhou²

From the Department of Pharmacology, University of California, Irvine, California 92697, the Departments of Psychiatry, Biobehavioral Sciences, and Molecular Pharmacology, University of California, Los Angeles, California 90095, and the ^¶Howard Hughes Medical Institute and Division of Biology, California Institute of Technology, Pasadena, California 91125

Prokineticin 2, a cysteine-rich secreted protein, regulates diverse biological functions including the neurogenesis of olfactory bulb. Here we show that the PK2 gene is a functional target gene of proneural basic helix-loop-helix (bHLH) factors. Neurogenin 1 and MASH1 activate PK2 transcription by binding to E-box motifs on the PK2 promoter with the same set of E-boxes critical for another pair of bHLH factors, CLOCK and BMAL1, in the regulation of circadian clock. Our results establish PK2 as a common functional target gene for different bHLH transcriptional factors in mediating their respective functions.

Received for publication, November 15, 2006 , and in revised form, January 17, 2007.

^* The work was supported in part by a University of California Discovery grant. 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 four supplemental figures.

¹ A recipient of a University of California Irvine Medical Scientist Training Program training grant.

² To whom correspondence should be addressed. Tel.: 949-824-2232; Fax: 949-824-4855; E-mail: qzhou{at}uci.edu.

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