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GCN5 acetyltransferase inhibits PGC1alpha-induced hepatitis B virus biosynthesis.

Authors: Tian, X  Zhao, F  Cheng, Z  Zhou, M  Zhi, X  Li, J  Hu, K 
Citation: Tian X, etal., Virol Sin. 2013 Aug;28(4):216-22. doi: 10.1007/s12250-013-3344-3. Epub 2013 Jul 2.
Pubmed: (View Article at PubMed) PMID:23913178
DOI: Full-text: DOI:10.1007/s12250-013-3344-3

Hepatitis B virus (HBV) biosynthesis is primarily restricted to hepatocytes due to the governing of liver-enriched nuclear receptors (NRs) on viral RNA synthesis. The liver-enriched NR hepatocyte nuclear factor 4alpha (HNF4alpha), the key regulator of genes implicated in hepatic glucose metabolism, is also a primary determinant of HBV pregenomic RNA synthesis and HBV replication. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC1alpha) coactivates and further enhances the effect of HNF4alpha on HBV biosynthesis. Here, we showed that the acetyltransferase General Control Non-repressed Protein 5 (GCN5) acetylated PGC1alpha, leading to alteration of PGC1alpha from a transcriptionally active state into an inactive state. As a result, the coactivation activity of PGC1alpha on HBV transcription and replication was suppressed. Apparently, an acetylation site mutant of PGC1alpha (PGC1alphaR13) still had coactivation activity as GCN5 could not suppress the coactivation activity of the mutant. Moreover, a catalytically inactive acetyltransferase mutant GCN5m, due to the loss of acetylation activity, failed to inhibit the coactivation function of PGC1alpha in HBV biosynthesis. Our results demonstrate that GCN5, through its acetyltransferase activity, inhibits PGC1alpha-induced enhancement of HBV transcription and replication both in vitro and in vivo.

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CRRD Object Information
CRRD ID: 9590262
Created: 2014-11-21
Species: All species
Last Modified: 2014-11-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.