ArticleJournal of virology2010
Role of noncovalent SUMO binding by the human cytomegalovirus IE2 transactivator in lytic growth.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Detangling knots: the intricate roles of G-quadruplexes in herpesvirus replication.Journal of virology · 2026Review
- Evidence for G-quadruplex-mediated transactivation by the immediate-early 2 protein of human cytomegalovirus.Journal of virology · 2025Article
- Review
- Article
- Virus-host protein interactions as footprints of human cytomegalovirus replication.Current opinion in virology · 2022Review
- Article
- Non-covalent Interaction With SUMO Enhances the Activity of Human Cytomegalovirus Protein IE1.Frontiers in cell and developmental biology · 2021Article
- The Promyelocytic Leukemia Protein facilitates human herpesvirus 6B chromosomal integration, immediate-early 1 protein multiSUMOylation and its localization at telomeres.PLoS pathogens · 2020Article
- Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II.PLoS pathogens · 2020Article
- Casein kinase-2-mediated phosphorylation increases the SUMO-dependent activity of the cytomegalovirus transactivator IE2.The Journal of biological chemistry · 2019Article
- A conserved and buried edge-to-face aromatic interaction in small ubiquitin-like modifier (SUMO) has a role in SUMO stability and function.The Journal of biological chemistry · 2019Article
- Allosteric Inhibition of Ubiquitin-like Modifications by a Class of Inhibitor of SUMO-Activating Enzyme.Cell chemical biology · 2019Article
- Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme.Nature communications · 2018Article
- Cooperative inhibition of RIP1-mediated NF-κB signaling by cytomegalovirus-encoded deubiquitinase and inactive homolog of cellular ribonucleotide reductase large subunit.PLoS pathogens · 2017Article
- The essential role of guinea pig cytomegalovirus (GPCMV) IE1 and IE2 homologs in viral replication and IE1-mediated ND10 targeting.Virology · 2017Article
- Viral Interplay with the Host Sumoylation System.Advances in experimental medicine and biology · 2017Review
- SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D To Facilitate Viral Replication.Journal of virology · 2016Article
- Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators.PLoS pathogens · 2016Article
- K-bZIP Mediated SUMO-2/3 Specific Modification on the KSHV Genome Negatively Regulates Lytic Gene Expression and Viral Reactivation.PLoS pathogens · 2015Article
- Biphasic regulation of A20 gene expression during human cytomegalovirus infection.Virology journal · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The 86-kDa immediate-early 2 (IE2) protein of human cytomegalovirus (HCMV) is a promiscuous transactivator essential for viral gene expression. IE2 is covalently modified by SUMO at two lysine residues (K175 and K180) and also interacts noncovalently with SUMO. Although SUMOylation of IE2 has been shown to enhance its transactivation activity, the role of SUMO binding is not clear. Here we showed that SUMO binding by IE2 is necessary for its efficient transactivation function and for viral growth. IE2 bound physically to SUMO-1 through a SUMO-interacting motif (SIM). Mutations in SIM (mSIM) or in both SUMOylation sites and SIM (KR/mSIM), significantly reduced IE2 transactivation effects on viral early promoters. The replication of IE2 SIM mutant viruses (mSIM or KR/mSIM) was severely depressed in normal human fibroblasts. Analysis of viral growth curves revealed that the replication defect of the mSIM virus correlated with low-level accumulation of SUMO-modified IE2 and of viral early and late proteins. Importantly, both the formation of viral transcription domains and the association of IE2 with viral promoters in infected cells were significantly reduced in IE2 SIM mutant virus infection. Furthermore, IE2 was found to interact with the SUMO-modified form of TATA-binding protein (TBP)-associated factor 12 (TAF12), a component of the TFIID complex, in a SIM-dependent manner, and this interaction enhanced the transactivation activity of IE2. Our data demonstrate that the interaction of IE2 with SUMO-modified proteins plays an important role for the progression of the HCMV lytic cycle, and they suggest a novel viral mechanism utilizing the cellular SUMO system.
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