Lin WJ |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=278 ------>confirm_bywho=shiemin ------>insert_bywho=yehsd ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=9360 ------>medlineContent= ------>unit=E0117 ------>insert_date=20041013 ------>iam=4 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=J. Biol. Chem. ------>paper_name=Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4. ------>confirm_date=20050517 ------>tch_id=091054 ------>pmid=12522137 ------>page1=9353 ------>fullAbstract=The TR4 orphan receptor is a member of the nuclear receptor superfamily that modulates gene expression via binding to the AGGTCA direct repeat hormone response element. Here we report a functional study of TR4 interaction with the core promoter of the hepatitis B virus (HBV). The electrophoretic mobility shift assay shows that TR4 can bind to the direct repeat 1 sequence element (AGGTTAAAGGTCT, nucleotide coordinates 1757-1769, TR4RE-HBV) on the HBV core promoter. TR4 also can enhance the activity of a synthetic luciferase reporter linked with four copies of TR4RE-HBV in either liver HepG2 or non-liver H1299 cells in a dose-dependent manner. Surprisingly, TR4 represses the activity of a luciferase reporter containing the entire HBV genome sequences. Moreover, mutation of this TR4RE-HBV site in the HBV core promoter diminishes the TR4 suppression effect. This TR4-induced suppression of HBV core promoter activity is further confirmed by primer extension analysis of the HBV core RNAs, showing that TR4 represses both pre-core and core mRNAs. Further dissection of this repressive mechanism indicates that TR4 may suppress the HBV core promoter activity via repressing HNF4alpha-mediated transactivation by protein-protein interactions without inhibition of HNF4alpha DNA binding. Furthermore, our results indicate that the N- and C-terminal regions of TR4 protein are required for TR4-HNF4alpha interaction. It is possible that TR4-HNF4alpha interaction may block the HNF4alpha function that results in the suppression of HBV gene expression. Together, these results demonstrate that TR4 can serve as a negative modulator in the transcriptional regulation of HBV core gene expression. ------>tmu_sno=None ------>sno=9817 ------>authors2=Li J ------>authors3=Lee YF ------>authors4=Yeh SD ------>authors5=Altuwaijri S ------>authors6=Ou JH, Chang C ------>authors6_c=None ------>authors=Lin WJ ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Suppression of hepatitis B virus core promoter by the nuclear orphan receptor TR4. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=11 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2003 ------>submit_flag=None ------>publish_month=None |