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.
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.
Yang
Liuqing
L
Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.
Lin
Chunru
C
Zhao
Shumin
S
Wang
Haizhen
H
Liu
Zhi-Ren
ZR
D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D019938:Cyclin D1 / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D017931:DNA Primers; D016259:Genes, myc; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D019938:Cyclin D1; D053487:DEAD-box RNA Helicases