title: 14-3-3ζ interacts with hepatocyte nuclear factor 1α and enhances its DNA binding and transcriptional activation.
abstract: 14-3-3 proteins regulate numerous cellular processes through interaction with a variety of proteins, and have been identified as HNF1α binding partner by mass spectrometry analysis in our previous study. In the present study, the interaction between 14-3-3ζ and HNF1α has been further validated by in vivo and in vitro assays. Moreover, we have found that overexpression of 14-3-3ζ potentiated the transcriptional activity of HNF1α in cultured cells, and silencing of 14-3-3ζ by RNA interference in HepG2 cells specifically affected the HNF1α-dependent gene expression. Furthermore, we have demonstrated that 14-3-3ζ is recruited to endogenous HNF1α responsive promoters and enhances HNF1α binding to its cognate DNA sequences. In addition, we have also provided evidence that the association between HNF1α and 14-3-3ζ is phosphorylation-dependent. Taken together, these results suggest that 14-3-3ζ may be an endogenous physiologic regulator of HNF1α.
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Heng-Xi
authors.initials: HX
authors.lastname: Guo
authors.lastname: Hui-Chen
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Li
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Zhan
authors.forename: Chang-Hui
authors.initials: CH
authors.lastname: Ge
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Yang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
chemical_list: D048948:14-3-3 Proteins; D017931:DNA Primers; D051538:Hepatocyte Nuclear Factor 1-alpha; C572235:YWHAZ protein, human; D004247:DNA
keywords: 14-3-3; 14-3-3zeta; 14-3-3ζ; CIP; ChIP; EMSA; FRET; HNF; HNF1α; MODY; OA; Phosphorylation; Transcription regulation; calf intestinal alkaline phosphatase; chromatin-immunoprecipitation; electrophoretic mobility shift assay; fluorescence resonance energy transfer; hepatocyte nuclear factor; maturity onset diabetes of the young; okadaic acid