title: Phosphorylated p68 RNA helicase activates Snail1 transcription by promoting HDAC1 dissociation from the Snail1 promoter.
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.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Carter
authors.forename: C
authors.initials: C
authors.lastname: Lin
authors.forename: C-Y
authors.initials: CY
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: Z-R
authors.initials: ZR
authors.lastname: Liu
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D056284:Histone Deacetylase 1 / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D010982:Platelet-Derived Growth Factor; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D012313:RNA; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D053487:DEAD-box RNA Helicases