Kaposi's Sarcoma-Associated Herpesvirus K-bZIP Represses Gene Transcription via SUMO Modification

Department of Biological Chemistry, University of California--Davis (UC Davis), School of Medicine, Sacramento, 95817, USA.
Journal of Virology (Impact Factor: 4.65). 09/2005; 79(15):9912-25. DOI: 10.1128/JVI.79.15.9912-9925.2005
Source: PubMed

ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus implicated in AIDS-related neoplasms. Previously, we demonstrated that the early lytic gene product K-bZIP is a transcriptional repressor that affects a subset of viral gene transcriptions mediated by the viral transactivator K-Rta (Y. Izumiya et al. J. Virol. 77:1441-1451, 2003). Sumoylation has emerged as an important posttranslational modification that affects the location and function of cellular and viral proteins and also plays a significant role in transcriptional repression along with Ubc9, the E2 SUMO conjugation enzyme. Here, we provide evidence that K-bZIP is sumoylated at the lysine 158 residue and associates with Ubc9 both in a cell-free system and in virus-infected BCBL-1 cells. Reporter assays showed that the expression of SUMO-specific protease 1 attenuated the transcriptional repression activity of K-bZIP. The expression of a K-bZIPK158R mutant, which was no longer sumoylated, exhibited the reduced transcriptional repression activity. This indicates that sumoylation plays an important part in the transcriptional repression activity of K-bZIP. Finally, chromatin immunoprecipitation experiments demonstrated that K-bZIP interacts with and recruits Ubc9 to specific KSHV promoters. Thus, our data indicate that K-bZIP is a SUMO adaptor, which recruits Ubc9 to specific viral target promoters, thereby exerting its transcriptional repression activity.

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Available from: Hsing-Jien Kung, Nov 28, 2014
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    • "K-bZIP directly associates with K-Rta in KSHV infected cells and represses K-Rta-mediated transactivation at a subset of KSHV promoters. This activity of K-bZIP is subject to post-translational modulation via phosphorylation (Izumiya et al., 2007) and sumoylation (Izumiya et al., 2005). As detailed below, K-bZIP repression activity on K-Rta-mediated transactivation is regulated in an opposing manner by these two post-translational modifications. "
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    • "This is likely to be the case for splice variant IV. The reason why Izumiya et al. (2005) have missed this site is because the expression vector that they have used expresses a fully spliced variant of K8. For our studies, we have cloned a genomic segment of the KSHV genome allowing the multiple spliced transcripts to be expressed, as it is the case during a natural infection. "
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    • "Poly(ADP-ribose) polymerase 1 (PARP-1) and a kinase, hKFC interacts with RTA to ribosylate and phosphorylate which reduces the transcriptional activity of RTA by abolishing binding to RRE (Gwack et al., 2003). Sumoylation of K-bZIP also plays a role in modulating k-bZIP-mediated RTA activation of KSHV-specific promoters (Izumiya et al., 2005). These studies propose that posttranslation modifications of viral proteins are required to regulate KSHV lytic replication. "
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