https://scholars.lib.ntu.edu.tw/handle/123456789/568627
Title: | ERK1/2-mediated phosphorylation of small hepatitis delta antigen at serine 177 enhances hepatitis delta virus antigenomic RNA replication | Authors: | Chen Y.-S. Huang W.-H. Hong S.-Y. Tsay Y.-G. PEI-JER CHEN |
Issue Date: | 2008 | Publisher: | American Society for Microbiology | Journal Volume: | 82 | Journal Issue: | 19 | Start page/Pages: | 9345-9358 | Source: | Journal of Virology | Abstract: | The small hepatitis delta virus (HDV) antigen (SHDAg) plays an essential role in HDV RNA double-rolling-circle replication. Several posttranslational modifications (PTMs) of HDAgs, including phosphorylation, acetylation, and methylation, have been characterized. Among the PTMs, the serine 177 residue of SHDAg is a phosphorylation site, and its mutation preferentially abolishes HDV RNA replication from antigenomic RNA to genomic RNA. Using coimmunoprecipitation analysis, the cellular kinases extracellular signal-related kinases 1 and 2 (ERK1/2) are found to be associated with the Flag-tagged SHDAg mutant (Ser-177 replaced with Cys-177). In an in vitro kinase assay, serine 177 of SHDAg was phosphorylated directly by either Flag-ERK1 or Flag-ERK2. Activation of endogenous ERK1/2 by a constitutively active MEK1 (hemagglutinin-AcMEK1) increased phosphorylation of SHDAg at Ser-177; this phosphorylation was confirmed by immunoblotting using an antibody against phosphorylated S177 and mass spectrometric analysis. Interestingly, we found an increase in the HDV replication from antigenomic RNA to genomic RNA but not in that from genomic RNA to antigenomic RNA. The Ser-177 residue was critical for SHDAg interaction with RNA polymerase II (RNAPII), the enzyme proposed to regulate antigenomic RNA replication. These results demonstrate the role of ERK1/2-mediated Ser-177 phosphorylation in modulating HDV antigenomic RNA replication, possibly through RNAPII regulation. The results may shed light on the mechanisms of HDV RNA replication. Copyright ? 2008, American Society for Microbiology. All Rights Reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983726730&doi=10.1128%2fJVI.00656-08&partnerID=40&md5=2e3c68caf79a1e270327c56d4f1722b4 https://scholars.lib.ntu.edu.tw/handle/123456789/568627 |
ISSN: | 0022-538X | DOI: | 10.1128/JVI.00656-08 | SDG/Keyword: | cysteine; genomic RNA; hemagglutinin; hepatitis delta antigen; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase kinase 1; RNA polymerase II; serine; virus RNA; article; controlled study; enzyme activation; enzyme assay; Hepatitis delta virus; human; human cell; immunoblotting; immunoprecipitation; in vitro study; liquid chromatography; priority journal; protein interaction; protein phosphorylation; RNA replication; tandem mass spectrometry; virus replication; Hepatitis delta virus |
Appears in Collections: | 臨床醫學研究所 |
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