ArticlePloS one2014
Analysis of human cytomegalovirus-encoded SUMO targets and temporal regulation of SUMOylation of the immediate-early proteins IE1 and IE2 during infection.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Impact of emerging and re-emerging viral infections on periodontitis progression.Archives of microbiology · 2025Review
- Liver X Receptor-Growth Differentiation Factor 15 Activation Drives Profibrotic Changes in the Aqueous Outflow Tract of Uveitic Glaucoma.The American journal of pathology · 2025Article
- G-quadruplex as an essential structural element in cytomegalovirus replication origin.Nature communications · 2024Article
- Review
- Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome.International journal of molecular sciences · 2022Article
- Sumoylation of the Carboxy-Terminal of Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Attenuates Viral DNA Replication.Frontiers in microbiology · 2021Article
- A Tale of Usurpation and Subversion: SUMO-Dependent Integrity of Promyelocytic Leukemia Nuclear Bodies at the Crossroad of Infection and Immunity.Frontiers in cell and developmental biology · 2021Review
- Revisiting promyelocytic leukemia protein targeting by human cytomegalovirus immediate-early protein 1.PLoS pathogens · 2020Article
- Bright and Early: Inhibiting Human Cytomegalovirus by Targeting Major Immediate-Early Gene Expression or Protein Function.Viruses · 2020Review
- Degradation of SAMHD1 Restriction Factor Through Cullin-Ring E3 Ligase Complexes During Human Cytomegalovirus Infection.Frontiers in cellular and infection microbiology · 2020Article
- B Cell Receptor Activation and Chemical Induction Trigger Caspase-Mediated Cleavage of PIAS1 to Facilitate Epstein-Barr Virus Reactivation.Cell reports · 2017Article
- Viral manipulation of the cellular sumoylation machinery.Cell communication and signaling : CCS · 2017Review
- The ND10 Component Promyelocytic Leukemia Protein Acts as an E3 Ligase for SUMOylation of the Major Immediate Early Protein IE1 of Human Cytomegalovirus.Journal of virology · 2017Article
- The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting.Virology · 2017Article
- Human Cytomegalovirus IE2 86 kDa Protein Induces STING Degradation and Inhibits cGAMP-Mediated IFN-β Induction.Frontiers in microbiology · 2017Article
- Viral Interplay with the Host Sumoylation System.Advances in experimental medicine and biology · 2017Review
- Orthoreovirus outer-fiber proteins are substrates for SUMO-conjugating enzyme Ubc9.Oncotarget · 2016Article
- Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators.PLoS pathogens · 2016Article
- Involvement of the N-Terminal Deubiquitinating Protease Domain of Human Cytomegalovirus UL48 Tegument Protein in Autoubiquitination, Virion Stability, and Virus Entry.Journal of virology · 2016Article
- HCMV Displays a Unique Transcriptome of Immunomodulatory Genes in Primary Monocyte-Derived Cell Types.PloS one · 2016Article
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Authors and funding
6 authors.
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Abstract
Post-translational modification of proteins by members of the small ubiquitin-like modifier (SUMO) is involved in diverse cellular functions. Many viral proteins are SUMO targets and also interact with the cellular SUMOylation system. During human cytomegalovirus (HCMV) infection, the immediate-early (IE) proteins IE1 and IE2 are covalently modified by SUMO. IE2 SUMOylation promotes its transactivation activity, whereas the role of IE1 SUMOylation is not clear. We performed in silico, genome-wide analysis to identify possible SUMOylation sites in HCMV-encoded proteins and evaluated their modification using the E. coli SUMOylation system and in vitro assays. We found that only IE1 and IE2 are substantially modified by SUMO in E. coli, although US34A was also identified as a possible SUMO target in vitro. We also found that SUMOylation of IE1 and IE2 is temporally regulated during viral infection. Levels of SUMO-modified form of IE1 were increased during the early phase of infection, but decreased in the late phase when IE2 and its SUMO-modified forms were expressed at high levels. IE2 expression inhibited IE1 SUMOylation in cotransfection assays. As in IE2 SUMOylation, PIAS1, a SUMO E3 ligase, interacted with IE1 and enhanced IE1 SUMOylation. In in vitro assays, an IE2 fragment that lacked covalent and non-covalent SUMO attachment sites, but was sufficient for PIAS1 binding, effectively inhibited PIAS1-mediated SUMOylation of IE1, indicating that IE2 expression negatively regulates IE1 SUMOylation. We also found that the IE2-mediated downregulation of IE1 SUMOylation correlates with the IE1 activity to repress the promoter containing the interferon stimulated response elements. Taken together, our data demonstrate that IE1 and IE2 are the main viral SUMO targets in HCMV infection and that temporal regulation of their SUMOylation may be important in the progression of this infection.
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