Abstract
The nuclear p68 RNA helicase is a prototypical member of the DEAD-box family of RNA helicases. p68 RNA helicase has been implicated in cell proliferation and early organ development and maturation. However, the functional role of p68 RNA helicase in these biological processes at the molecular level is not well understood. We previously reported that tyrosine phosphorylation of p68 RNA helicase mediates the effects of platelet-derived growth factor (PDGF) in induction of epithelial mesenchymal transition by promoting β-catenin nuclear translocation. Here, we report that phosphorylation of p68 RNA helicase at Y593 upregulates transcription of the Snail1 gene. The phosphorylated p68 activates transcription of the Snail1 gene by promoting histone deacetylase (HDAC)1 dissociation from the Snail1 promoter. Our results showed that p68 interacted with the nuclear remodeling and deacetylation complex MBD3:Mi-2/NuRD. Thus, our data suggested that a DEAD-box RNA unwindase could potentially regulate gene expression by functioning as a protein ‘displacer’ to modulate protein–protein interactions at the chromatin-remodeling complex.
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Acknowledgements
We thank Roger Bridgeman for antibody p68-rgg production. We also thank Birgit Neuhaus for assistance in confocal imaging. This paper is greatly improved by critical comments from Jenny Yang, Mike Kirberger, Julian A. Johnson and Heena Dey. This study is supported in part by Research Grants from National Institute of Health (GM063874), (CA118113) and Georgia Cancer Coalition to ZR Liu.
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Carter, C., Lin, C., Liu, CY. et al. Phosphorylated p68 RNA helicase activates snail1 transcription by promoting HDAC1 dissociation from the snail1 promoter. Oncogene 29, 5427–5436 (2010). https://doi.org/10.1038/onc.2010.276
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DOI: https://doi.org/10.1038/onc.2010.276
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