文摘
14-3-3 proteins regulate numerous cellular processes through interaction with a variety of proteins, and have been identified as HNF1¦Á binding partner by mass spectrometry analysis in our previous study. In the present study, the interaction between 14-3-3¦Æ and HNF1¦Á has been further validated by in vivo and in vitro assays. Moreover, we have found that overexpression of 14-3-3¦Æ potentiated the transcriptional activity of HNF1¦Á in cultured cells, and silencing of 14-3-3¦Æ by RNA interference in HepG2 cells specifically affected the HNF1¦Á-dependent gene expression. Furthermore, we have demonstrated that 14-3-3¦Æ is recruited to endogenous HNF1¦Á responsive promoters and enhances HNF1¦Á binding to its cognate DNA sequences. In addition, we have also provided evidence that the association between HNF1¦Á and 14-3-3¦Æ is phosphorylation-dependent. Taken together, these results suggest that 14-3-3¦Æ may be an endogenous physiologic regulator of HNF1¦Á.
