ArticleJournal of virology2017
Effects of the NEDD8-Activating Enzyme Inhibitor MLN4924 on Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus.
Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- FBXO11 and FBXO32 are associated with TRAF3-TBK1-IRF3 signaling components in chronic hepatitis B: evidence from clinical samples and preliminary mechanistic studies.American journal of translational research · 2026Article
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Caspase-Mediated Cleavage of the Transcription Factor Sp3: Possible Relevance to Cancer and the Lytic Cycle of Kaposi's Sarcoma-Associated Herpesvirus.Microbiology spectrum · 2022Article
- miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos.PeerJ · 2022Article
- Association Between Neddylation and Immune Response.Frontiers in cell and developmental biology · 2022Review
- Identification and Characterization of Human Norovirus NTPase Regions Required for Lipid Droplet Localization, Cellular Apoptosis, and Interaction with the Viral P22 Protein.Microbiology spectrum · 2021Article
- Sp3 Transcription Factor Cooperates with the Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein To Synergistically Activate Specific Viral and Cellular Gene Promoters.Journal of virology · 2020Article
- Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses.International journal of molecular sciences · 2019Review
- Subcellular Localization and Functional Characterization of GII.4 Norovirus-Encoded NTPase.Journal of virology · 2018Article
- Regulation of Cellular Antiviral Signaling by Modifications of Ubiquitin and Ubiquitin-like Molecules.Immune network · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The switch of Kaposi's sarcoma-associated herpesvirus (KSHV) from latency to lytic replication is a key event for viral dissemination and pathogenesis. MLN4924, a novel neddylation inhibitor, reportedly causes the onset of KSHV reactivation but impairs later phases of the viral lytic program in infected cells. Thus far, the molecular mechanism involved in the modulation of the KSHV lytic cycle by MLN4924 is not yet fully understood. Here, we confirmed that treatment of different KSHV-infected primary effusion lymphoma (PEL) cell lines with MLN4924 substantially induces viral lytic protein expression. Due to the key role of the virally encoded ORF50 protein in the latent-to-lytic switch, we investigated its transcriptional regulation by MLN4924. We found that MLN4924 activates the ORF50 promoter (ORF50p) in KSHV-positive cells (but not in KSHV-negative cells), and the RBP-Jκ-binding elements within the promoter are critically required for MLN4924 responsiveness. In KSHV-negative cells, reactivation of the ORF50 promoter by MLN4924 requires the presence of the latency-associated nuclear antigen (LANA). Under such a condition, LANA acts as a repressor to block the ORF50p activity, whereas MLN4924 treatment relieves LANA-mediated repression. Importantly, we showed that LANA is a neddylated protein and can be deneddylated by MLN4924. On the other hand, we revealed that MLN4924 exhibits concentration-dependent biphasic effects on 12-
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