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J. Biol. Chem., Vol. 282, Issue 23, 16811-16819, June 8, 2007

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Phosphorylation of p68 RNA Helicase Plays a Role in Platelet-derived Growth Factor-induced Cell Proliferation by Up-regulating Cyclin D1 and c-Myc Expression^*

From the Department of Biology, Georgia State University, Atlanta, Georgia 30303

p68 RNA helicase is a protypical member of DEAD box family RNA helicase. The protein plays an important role in the cell developmental program and organ maturation. We demonstrated previously that, in response to growth factor platelet-derived growth factor (PDGF)-BB stimulation, p68 is phosphorylated at Tyr⁵⁹³, and the phosphorylation of p68 promotes epithelial-mesenchymal transition via promoting -catenin nuclear translocation (Yang, L., Lin, C., and Liu, Z. R. (2006) Cell 127, 139–155). We show here that the tyrosine phosphorylation of p68 also mediates the effects of PDGF in stimulating cell proliferation. The phosphorylated p68 (referred to as phospho-p68) promotes cell proliferation by activating the transcription of cyclin D1 and c-Myc genes. We show that the ATPase/helicase activities of p68 are required for the activation of cyclin D1 transcription. The phospho-p68 participates in the complex assembled at the cyclin D1 and c-Myc promoters, which strongly suggests a direct role in transcriptional regulation. Furthermore, our data demonstrated that the phosphorylation of p68 at Tyr⁵⁹³ plays a role in mediating the autocrine loop effects of PDGF, suggesting an important role for p68 phosphorylation in cell proliferation.

Received for publication, November 10, 2006 , and in revised form, March 22, 2007.

^* This work was supported in part by National Institute of Health Grant GM063874 and a research grant from the Georgia Cancer Coalition (to Z.-R. L.). 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 Supported by a Molecular Base of Disease (MBD) fellowship.

² To whom correspondence should be addressed: Dept. of Biology, Georgia State University, University Plaza Atlanta, GA 30303. Tel.: 404-463-9919; Fax: 404-651-2509; E-mail: biozrl{at}langate.gsu.edu.

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