ArticleOncogene2003
Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 121 citations in OpenAlex.
- The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells.PLoS pathogens · 2013Trial
- Dendritic Cells Derived MMP9 Fuels Sepsis-Induced Cardiac Dysfunction Through JNK/AP1 Driven Pro-Inflammatory Cytokine and Nitric Oxide Storm.Inflammation · 2026Article
- The role of pioneering transcription factors, chromatin accessibility and epigenetic reprogramming in oncogenic viruses.Frontiers in microbiology · 2025Review
- Article
- Targeting Kaposi's sarcoma associated herpesvirus encoded protease (ORF17) by a lysophosphatidic acid molecule for treating KSHV associated diseases.Frontiers in cell and developmental biology · 2023Article
- Cancers associated with human gammaherpesviruses.The FEBS journal · 2022Review
- Nm23-H1 induces apoptosis in primary effusion lymphoma cells via inhibition of NF-κB signaling through interaction with oncogenic latent protein vFLIP K13 of Kaposi's sarcoma-associated herpes virus.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Oncologic Treatment of HIV-Associated Kaposi Sarcoma 40 Years on.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Review
- Worenine Prevents Solar Ultraviolet-Induced Sunburn by Inhibiting JNK2.Frontiers in pharmacology · 2022Article
- Castleman disease.Nature reviews. Disease primers · 2021Review
- The anti-malaria agent artesunate exhibits cytotoxic effects in primary effusion lymphoma.Investigational new drugs · 2021Article
- Lenalidomide in Combination with Arsenic Trioxide: an Effective Therapy for Primary Effusion Lymphoma.Cancers · 2020Article
- Sperm associated antigen 9 promotes oncogenic KSHV-encoded interferon regulatory factor-induced cellular transformation and angiogenesis by activating the JNK/VEGFA pathway.PLoS pathogens · 2020Article
- Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure.Cell death & disease · 2019Article
- C19ORF66 Broadly Escapes Virus-Induced Endonuclease Cleavage and Restricts Kaposi's Sarcoma-Associated Herpesvirus.Journal of virology · 2019Article
- Kaposi sarcoma herpesvirus pathogenesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- HIV-associated Kaposi sarcoma and related diseases.AIDS (London, England) · 2017Review
- Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases.PLoS pathogens · 2017Article
- Article
- Kaposi sarcoma herpesvirus-associated cancers and related diseases.Current opinion in HIV and AIDS · 2017Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a FADD-like interferon converting enzyme or caspase 8 (FLICE) inhibitory protein (vFLIP) that prevents death receptor-mediated apoptosis by inhibiting the recruitment and activation of FLICE. Since vFLIP physically interacts with tumor necrosis factor receptor associated factor 2 (TRAF2) and TRAF2 mediates activation of the jun NH(2)-terminal kinase (JNK)/activation protein 1 (AP1) pathway, we hypothesized that vFLIP might also activate this pathway. To evaluate this hypothesis, we transiently and stably transfected a vFLIP expression construct and performed several complementary assays to document that vFLIP activates the JNK/AP1 pathway and does so in a TRAF-dependent fashion. As vFLIP also activates the nuclear factor kappaB (NF-kappaB) signaling pathway and the NF-kappaB and JNK/AP1 pathways both modulate cellular interleukin-6 (cIL-6) expression, we postulated that vFLIP induces expression of this cytokine. We show that vFLIP induces cIL-6 expression and activates the cIL-6 promoter, and maximal activation of the cIL-6 promoter by vFLIP requires NF-kappaB and AP1 activation. In addition, vFLIP and latency-associated nuclear antigen (LANA), another KSHV-encoded latent protein, potentiate each other's ability to activate the cIL-6 promoter. Gene silencing experiments by RNA interference demonstrate that vFLIP in BCBL-1 endogenously infected primary effusion lymphoma (PEL) cells mediates JNK/AP1 activation and cIL-6 expression. Thus, we conclude that vFLIP, in addition to its known effects on NF-kappaB activation, also modulates the JNK/AP1 pathway and induces gene expression from the cIL-6 promoter in a JNK/AP1-dependent fashion.
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Registered trials
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.