2002
DOI: 10.1074/jbc.m200613200
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The Double-stranded RNA-activated Kinase, PKR, Can Phosphorylate Hepatitis D Virus Small Delta Antigen at Functional Serine and Threonine Residues

Abstract: Hepatitis D virus (HDV) encodes two proteins, the 24-kDa small delta antigen (S-HDAg) and 27-kDa large delta antigen (L-HDAg) in its single open reading frame. Both of them had been identified as nuclear phosphoproteins. Moreover, the phosphorylated form of S-HDAg was shown to be important for HDV replication. However, the kinase responsible for S-HDAg phosphorylation remains unknown. Therefore, we employed an ingel kinase assay to search candidate kinases and indeed identified a kinase with a molecular mass o… Show more

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Cited by 42 publications
(33 citation statements)
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“…Nevertheless, these results combined support the conclusion that methylation is essential for HDV RNA replication. Previously, it was demonstrated that the phosphorylation and acetylation of HDAg are essential for HDV RNA replication (6,35,36). Thus, multiple types of posttranslational modifications of S-HDAg are required for HDV RNA replication.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Nevertheless, these results combined support the conclusion that methylation is essential for HDV RNA replication. Previously, it was demonstrated that the phosphorylation and acetylation of HDAg are essential for HDV RNA replication (6,35,36). Thus, multiple types of posttranslational modifications of S-HDAg are required for HDV RNA replication.…”
Section: Discussionmentioning
confidence: 99%
“…The phosphorylation of HDAg occurs at multiple residues, with Serine-177 (S-177) being the major phosphorylation site (3,35). S-177 phosphorylation is required for efficient viral RNA replication, particularly for replication of the antigenomic RNA strand (6,35). Recently, the acetylation of HDAg was reported (36), and this process is also involved in the replication of HDV RNA and may regulate the subcellular localization of HDAg.…”
mentioning
confidence: 99%
“…We also note that although Pol I had been implicated in HDV replication based on drug inhibition and HDV localization studies (Modahl et al 2000;Macnaughton et al 2002), no Pol I-(or Pol III-) specific subunits were detected. Another validation for this proteomic approach is that SPT5 (part of DSIF) and PKR, two previously identified HDAg-S interacting proteins (Yamaguchi et al 2001;Chen et al 2002), were also identified by this approach. Interestingly, hnRNP D and ZNF326, whose abundance was changed as a result of HDAg-S transient transfection in a previous proteomics screen (Mota et al 2008), were also identified as HDAg-S interacting proteins here.…”
Section: Identification Of Hdag Interacting Proteins By Immunoprecipimentioning
confidence: 99%
“…The Pol I specific factor SL1 (Li et al 2006) and the negative transcription elongation factor DSIF (Yamaguchi et al 2001) have also been demonstrated to interact with HDAg, but their effect on HDV replication in vivo is not clear. A double-stranded RNA-activated kinase, PKR, has been shown to bind to HDAg-S (Chen et al 2002) and HDV RNA (Robertson et al 1996;Circle et al 1997), and affect HDV replication (Chen et al 2002). Finally, GAPDH was reported to bind to HDV RNA (Lin et al 2000), and ADAR1 was found to edit HDV antigenomic RNA (Wong and Lazinski 2002).…”
Section: Introductionmentioning
confidence: 99%
“…We observed 2.5-fold activation by p27 but not by p24 (data not shown). As HDV replication involves the action of IFN-a-inducedproteins, such as PKR (Chen et al, 2002), and as we showed that the MxA protein was involved in inhibition of HBV replication (Gordien et al, 2001), we questioned whether p24 and/or p27 could interfere with this pathway. Co-transfection experiments were performed using the pMxA 550 luciferase construct.…”
Section: Involvement Of Fpv Within the Enh1 Core Region In Enh1 Inhibmentioning
confidence: 99%