{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu Z"],"funding":["Shanghai Municipal Health Commission","Shanghai Frontiers Science Center of Cellular Homeostasis and Human Disease","NIDCR NIH HHS","Innovative Research Team of High-level Local Universities in Shanghai","National Institutes of Health","National Key Research and Development Project of China","Shanghai Science and Technology Commission","Shanghai Sailing Program"],"pagination":["e1010504"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9089915"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(4)"],"pubmed_abstract":["RSK1, an essential cellular kinase for Kaposi's sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosph"],"journal":["PLoS pathogens"],"pubmed_title":["The SUMO E3 ligase activity of ORF45 determines KSHV lytic replication."],"pmcid":["PMC9089915"],"funding_grant_id":["R01 DE016680","R01DE026101","20YF1442500","22ZR1454500","R01 DE026101","20204Y0347","2018YFA0900802","201940179","R01DE016680"],"pubmed_authors":["Li W","Liu Z","Wang C","Zhang Y","Fu J","Zhu F","Wang X","Liu C","Xu X","Xiao MZX","Deng H","Liang Q"],"additional_accession":[]},"is_claimable":false,"name":"The SUMO E3 ligase activity of ORF45 determines KSHV lytic replication.","description":"RSK1, an essential cellular kinase for Kaposi's sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosph","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-04T19:10:31.72Z","creation":"2025-04-04T19:10:31.72Z"},"accession":"S-EPMC9089915","cross_references":{"pubmed":["35482828"],"doi":["10.1371/journal.ppat.1010504"]}}