ArticlePLoS pathogens2015
NEDDylation is essential for Kaposi's sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- Epidemiology, molecular typing, microbiome-immune interactions and treatment strategies of endometrial cancer: a review.Frontiers in immunology · 2025Review
- Virus-modified paraspeckle-like condensates are hubs for viral RNA processing and their formation drives genomic instability.Nature communications · 2024Article
- B cell expression of E3 ubiquitin ligase Cul4b promotes chronic gammaherpesvirus infectionJournal of virology · 2023Article
- Effects of neddylation on viral infection: an overview.Archives of virology · 2023Review
- Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, sensitizes cancer cells to VSVΔ51 oncolytic virotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- mViruses · 2023Article
- Host Cell Neddylation Facilitates Alphaherpesvirus Entry in a Virus-Specific and Cell-Dependent Manner.Microbiology spectrum · 2022Article
- Association Between Neddylation and Immune Response.Frontiers in cell and developmental biology · 2022Review
- Multicentric Castleman disease and the evolution of the concept.Pathologica · 2021Review
- Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.Viruses · 2021Review
- The FAT10 post-translational modification is involved in the lytic replication of Kaposi's sarcoma-associated herpesvirus.Journal of virology · 2021Article
- The pivotal roles of neddylation pathway in immunoregulation.Immunity, inflammation and disease · 2020Review
- Role of Post-translational Modifications in Influenza A Virus Life Cycle and Host Innate Immune Response.Frontiers in microbiology · 2020Review
- Rational Engineering and Preclinical Evaluation of Neddylation and SUMOylation Site Modified Adeno-Associated Virus Vectors in Murine Models of Hemophilia B and Leber Congenital Amaurosis.Human gene therapy · 2019Article
- The Tudor SND1 protein is an meLife · 2019Article
- Cellular Cullin RING Ubiquitin Ligases: Druggable Host Dependency Factors of Cytomegaloviruses.International journal of molecular sciences · 2019Review
- Contribution of the KSHV and EBV lytic cycles to tumourigenesis.Current opinion in virology · 2018Review
- Cellular sheddases are induced by Merkel cell polyomavirus small tumour antigen to mediate cell dissociation and invasiveness.PLoS pathogens · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), which are aggressive malignancies associated with immunocompromised patients. For many non-viral malignancies, therapeutically targeting the ubiquitin proteasome system (UPS) has been successful. Likewise, laboratory studies have demonstrated that inhibition of the UPS might provide a promising avenue for the treatment of KSHV-associated diseases. The largest class of E3 ubiquitin ligases are the cullin-RING ligases (CRLs) that are activated by an additional ubiquitin-like protein, NEDD8. We show that pharmacological inhibition of NEDDylation (using the small molecule inhibitor MLN4924) is cytotoxic to PEL cells by inhibiting NF-κB. We also show that CRL4B is a novel regulator of latency as its inhibition reactivated lytic gene expression. Furthermore, we uncovered a requirement for NEDDylation during the reactivation of the KSHV lytic cycle. Intriguingly, inhibition prevented viral DNA replication but not lytic cycle-associated gene expression, highlighting a novel mechanism that uncouples these two features of KSHV biology. Mechanistically, we show that MLN4924 treatment precluded the recruitment of the viral pre-replication complex to the origin of lytic DNA replication (OriLyt). These new findings have revealed novel mechanisms that regulate KSHV latency and reactivation. Moreover, they demonstrate that inhibition of NEDDylation represents a novel approach for the treatment of KSHV-associated malignancies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.