O-GlcNAc transferase inhibits KSHV propagation and modifies replication relevant viral proteins as detected by systematic O-GlcNAcylation analysis.

Jochmann R, Pfannstiel J, Chudasama P, Kühn E, Konrad A, Stürzl M (2013)


Publication Status: Published

Publication Type: Journal article

Publication year: 2013

Journal

Book Volume: 23

Pages Range: 1114-30

Journal Issue: 10

DOI: 10.1093/glycob/cwt028

Abstract

O-GlcNAcylation is an inducible, highly dynamic and reversible post-translational modification, mediated by a unique enzyme named O-linked N-acetyl-d-glucosamine (O-GlcNAc) transferase (OGT). In response to nutrients, O-GlcNAc levels are differentially regulated on many cellular proteins involved in gene expression, translation, immune reactions, protein degradation, protein-protein interaction, apoptosis and signal transduction. In contrast to eukaryotic cells, little is known about the role of O-GlcNAcylation in the viral life cycle. Here, we show that the overexpression of the OGT reduces the replication efficiency of Kaposi's sarcoma-associated herpesvirus (KSHV) in a dose-dependent manner. In order to investigate the global impact of O-GlcNAcylation in the KSHV life cycle, we systematically analyzed the 85 annotated KSHV-encoded open reading frames for O-GlcNAc modification. For this purpose, an immunoprecipitation (IP) strategy with three different approaches was carried out and the O-GlcNAc signal of the identified proteins was properly controlled for specificity. Out of the 85 KSHV-encoded proteins, 18 proteins were found to be direct targets for O-GlcNAcylation. Selected proteins were further confirmed by mass spectrometry for O-GlcNAc modification. Correlation of the functional annotation and the O-GlcNAc status of KSHV proteins showed that the predominant targets were proteins involved in viral DNA synthesis and replication. These results indicate that O-GlcNAcylation plays a major role in the regulation of KSHV propagation.

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APA:

Jochmann, R., Pfannstiel, J., Chudasama, P., Kühn, E., Konrad, A., & Stürzl, M. (2013). O-GlcNAc transferase inhibits KSHV propagation and modifies replication relevant viral proteins as detected by systematic O-GlcNAcylation analysis. Glycobiology, 23(10), 1114-30. https://doi.org/10.1093/glycob/cwt028

MLA:

Jochmann, Ramona, et al. "O-GlcNAc transferase inhibits KSHV propagation and modifies replication relevant viral proteins as detected by systematic O-GlcNAcylation analysis." Glycobiology 23.10 (2013): 1114-30.

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