Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein

Kao, C. Cheng; Chen, Shiow Yi; Chen, Jeou Yuan; Lee, Yan-Hwa Wu

doi:10.1038/sj.onc.1207368

Cited by 113 publications

(93 citation statements)

References 76 publications

(58 reference statements)

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“…The integrity of each construct was verified by nucleotide sequencing. GST fusion proteins and His-tagged DDX3 were purified as described previously (You et al, 1999;Kao et al, 2004).…”

Section: Plasmids and Recombinant Proteinsmentioning

confidence: 99%

“…In vivo co-immunoprecipitation Whole lysates of HeLa cells were prepared as described previously (Kao et al, 2004). The cell extracts (1 mg) were then mixed with 20 mg of rabbit anti-eIF4E antiserum (Abcam, Cambridge, UK), rabbit anti-DDX3 antiserum (Chao et al, 2006) or preimmune rabbit serum and incubated with 20 ml of protein G beads for 2 h at 41C.…”

Section: In Vitro Translationmentioning

confidence: 99%

See 1 more Smart Citation

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein

Shih¹,

Tsai²,

Chao³

et al. 2007

Oncogene

156

197

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DDX3 is a human RNA helicase with plethoric functions. Our previous studies have indicated that DDX3 is a transcriptional regulator and functions as a tumor suppressor. In this study, we use a bicistronic reporter to demonstrate that DDX3 specifically represses cap-dependent translation but enhances hepatitis C virus internal ribosome entry site-mediated translation in vivo in a helicase activity-independent manner. To elucidate how DDX3 modulates translation, we identified translation initiation factor eukaryotic initiation factor 4E (eIF4E) as a DDX3-binding partner. Interestingly, DDX3 utilizes a consensus eIF4E-binding sequence YIPPHLR to interact with the functionally important dorsal surface of eIF4E in a similar manner to other eIF4E-binding proteins. Furthermore, cap affinity chromatography analysis suggests that DDX3 traps eIF4E in a translationally inactive complex by blocking interaction with eIF4G. Point mutations within the consensus eIF4E-binding motif in DDX3 impair its ability to bind eIF4E and result in a loss of DDX3's regulatory effects on translation. All these features together indicate that DDX3 is a new member of the eIF4E inhibitory proteins involved in translation initiation regulation. Most importantly, this DDX3-mediated translation regulation also confers the tumor suppressor function on DDX3. Altogether, this study demonstrates regulatory roles and action mechanisms for DDX3 in translation, cell growth and likely viral replication.

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“…The integrity of each construct was verified by nucleotide sequencing. GST fusion proteins and His-tagged DDX3 were purified as described previously (You et al, 1999;Kao et al, 2004).…”

Section: Plasmids and Recombinant Proteinsmentioning

confidence: 99%

Section: In Vitro Translationmentioning

confidence: 99%

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein

Shih¹,

Tsai²,

Chao³

et al. 2007

Oncogene

156

197

View full text Add to dashboard Cite

show abstract

“…Recently, inhibition of the TGF-b-pathway by direct interaction of the core protein with the DNAbinding domain of Smad3, important apoptosis mediators of TGF-b-receptor-I/II, has been demonstrated [65] . Several studies demonstrated binding of the HCV core protein to p53, either inhibiting or activating p53 [69,[78][79][80] with consecutive anti-or pro-apoptotic effects. In some studies apoptosis was inhibited in hepatoma through coredependent phosphorylation and activation of STAT3 that induces the anti-apoptotic bcl-XL [81,82] .…”

Section: Hcv Core Proteinmentioning

confidence: 99%

Hepatitis C virus infection and apoptosis

Fischer

Baumert²,

Blum³

2007

WJG

112

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“…In viewing of this, B23 may interact with this bipartite NLS of HCV core and transport HCV core into the nucleolus. Our previous work has also indicated that HCV core interacts with TBP and this interaction is required for the activation of RNA polymerase I transcription (Kao et al, 2004b). Conceivably, HCV core may be transported into the nucleolus by interacting with B23, where it activates RNA polymerase I transcription and this may result in higher rate of ribosome biogenesis.…”

Section: Discussionmentioning

confidence: 96%

Hepatitis C virus core protein recruits nucleolar phosphoprotein B23 and coactivator p300 to relieve the repression effect of transcriptional factor YY1 on B23 gene expression

Mai¹,

Yeh²,

Kao³

et al. 2005

Oncogene

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Hepatitis C virus (HCV) core has a pleiotropic effect on various promoters. In this study, we found that the expression of nucleolar phosphoprotein B23 was enhanced in HCV core-expressing cells and, moreover, HCV core interacts directly with the C-terminal end of B23. Using sucrose gradient centrifugation analysis and immunoprecipitation assays, HCV core was found in a large complex containing B23 and its interacting partner transcription factor YY1. Both B23 and HCV core associated with YY1 in the central GA/GK-rich and C-terminal zinc finger domain. These physical interactions between core, B23, and YY1 led to ternary complex formation that was bound to the YY1 response element. In a transient cotransfection experiment, relief of the transsuppression activity of YY1 on the YY1-response elementdriven reporter by core and B23 was found. This is also true when examining the effects of these three constructs on the B23 promoter-driven reporter. Additionally, chromatin immunoprecipitation assays indicated that a transcriptional activation complex consisting of core, together with B23, p300, and YY1, was recruited to the YY1 response element of B23 promoter, and this probably occurred through complex formation between core and these three cellular transcription regulators. This is different from the situation in the absence of core, where YY1 and histone deacetylase 1, but not B23 and p300, were associated on the YY1 element as the transcription repression complex. Together, our results indicate that HCV core can recruit B23 and p300 to relieve the repression effect of YY1 on B23 promoter activity, a property that requires the intrinsic histone acetyltransferase activity of p300. Thus, because these three core-associated cellular transcription regulators have a multitude of cellular interacting proteins and are involved in a versatility of cellular processes, the complex formation described here may partially account for the pleiotropic effects of core protein on gene expression and cellular function in HCV-infected cells.

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Modulation of p53 transcription regulatory activity and post-translational modification by hepatitis C virus core protein

Cited by 113 publications

References 76 publications

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein

Hepatitis C virus infection and apoptosis

Hepatitis C virus core protein recruits nucleolar phosphoprotein B23 and coactivator p300 to relieve the repression effect of transcriptional factor YY1 on B23 gene expression

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