Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication

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Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human tumor virus which hijacks the host signaling pathways in order to maintain persistent infection. We previously discovered that the KSHV protein ORF45 binds to and activates the cellular kinase RSK (p90 ribosomal S6 kinase), and that this activation is vital for optimal KSHV gene expression and virion production. Here, we performed a phosphoproteomic analysis of KSHV-infected cells to further characterize the specific substrates of ORF45-activated RSK. Bioinformatic analyses provided insights into the functional roles of these substrates. We verified the ORF45/RSK-dependent phosphorylation of a subset of these substrates by various means. Finally, we used genome editing to knock out RSK, as well as several cellular substrates identified by our screening, and characterized the consequent effect(s) on regulation of gene expression and virion production. Thus, this work further elucidates one of the key signaling nodes modulated by KSHV, and implicates ORF45-mediated activation of RSK in the regulation of viral and host gene expression during KSHV lytic replication.

Vyšlo v časopise: Phosphoproteomic Analysis of KSHV-Infected Cells Reveals Roles of ORF45-Activated RSK during Lytic Replication. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004993
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004993

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