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

Chunru Lin,Shumin Zhao,Liuqing Yang,Haizhen Wang,Zhi-Ren Liu

doi:10.1074/jbc.m610488200

Abstract

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 Tyr(593), and the phosphorylation of p68 promotes epithelial-mesenchymal transition via promoting beta-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 Tyr(593) plays a role in mediating the autocrine loop effects of PDGF, suggesting an important role for p68 phosphorylation in cell proliferation.

Highlights

Observed in a variety of human diseases, including glomerulosclerosis [1, 11] and diabetic proliferation retinopathy [12]
The Phospho-p68 Up-regulates Cyclin D1 and c-Myc and Promotes Cell Proliferation upon plateletderived growth factor (PDGF) Stimulation—We previously reported that p68 RNA helicase became phosphorylated at Tyr593 in HT-29 and HCT-116 cells by c-Abl upon PDGF-BB treatment
To test whether the phospho-p68 mediates the effects of PDGF in stimulating cell proliferation, we carried out cell proliferation assays using a commercially available cell proliferation kit that measures the incorporation of BrdUrd into cellular DNA in the proliferated cells

Summary

Introduction

Observed in a variety of human diseases, including glomerulosclerosis [1, 11] and diabetic proliferation retinopathy [12]. The phosphorylated p68 promotes cell proliferation by activating the transcription of cyclin D1 and c-Myc genes. The Phospho-p68 Up-regulates Cyclin D1 and c-Myc and Promotes Cell Proliferation upon PDGF Stimulation—We previously reported that p68 RNA helicase became phosphorylated at Tyr593 in HT-29 and HCT-116 cells by c-Abl upon PDGF-BB treatment.

Results

Conclusion