ArticleJournal of virology2014
Activation of NF-κB by the Kaposi's sarcoma-associated herpesvirus K15 protein involves recruitment of the NF-κB-inducing kinase, IκB kinases, and phosphorylation of p65.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity.Journal of virology · 2015Trial
- KSHV K15 genetic heterogeneity is associated with Kaposi sarcoma aggressiveness through modulation of the host inflammatory microenvironment.PLoS pathogens · 2026Article
- Host microRNA-31-5p regulates KHDRBS3 expression and modulates viral gene expression during KSHV lytic reactivation.Cell reports · 2026Article
- Recent Advances in the Histopathology, Molecular Biology, and Treatment of Kaposi Sarcoma: A Contemporary Review.International journal of molecular sciences · 2025Review
- Phenazine biosynthesis-like domain-containing protein (PBLD) and Cedrelone promote antiviral immune response by activating NF-ĸB.Nature communications · 2025Article
- Recruitment of phospholipase Cγ1 to the non-structural membrane protein pK15 of Kaposi Sarcoma-associated herpesvirus promotes its Src-dependent phosphorylation.PLoS pathogens · 2021Article
- Regulation of KSHV Latency and Lytic Reactivation.Viruses · 2020Review
- Association of NFκB and related-cytokines with the viral load and development of antibodies against HHV-8 in people living with HIV/AIDS.Medical microbiology and immunology · 2020Article
- The interplay between EBV and KSHV viral products and NF-κB pathway in oncogenesis.Infectious agents and cancer · 2020Review
- Expression of TLR4 gene is downregulated in acquired immune deficiency syndrome-associated Kaposi's sarcoma.Experimental and therapeutic medicine · 2019Article
- Kaposi's Sarcoma-Associated Herpesvirus Nonstructural Membrane Protein pK15 Recruits the Class II Phosphatidylinositol 3-Kinase PI3K-C2α To Activate Productive Viral Replication.Journal of virology · 2018Article
- Article
- Expression and Subcellular Localization of the Kaposi's Sarcoma-Associated Herpesvirus K15P Protein during Latency and Lytic Reactivation in Primary Effusion Lymphoma Cells.Journal of virology · 2017Article
- Kaposi sarcoma herpesvirus pathogenesis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers.Virologica Sinica · 2017Review
- The Kaposi's sarcoma-associated herpesvirus (KSHV) non-structural membrane protein K15 is required for viral lytic replication and may represent a therapeutic target.PLoS pathogens · 2017Article
- TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.Journal of cellular and molecular medicine · 2017Article
- A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma.Leukemia · 2017Article
- KSHV-Mediated Angiogenesis in Tumor Progression.Viruses · 2016Review
- Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway.Scientific reports · 2016Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledKaposi's sarcoma herpesvirus (KSHV) (or human herpesvirus 8) is the cause of Kaposi's sarcoma, primary effusion lymphoma (PEL), and the plasma cell variant of multicentric Castleman's disease (MCD). The transmembrane K15 protein, encoded by KSHV, has been shown to activate NF-κB and the mitogen-activated protein kinases (MAPKs) c-jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (Erk) as well as phospholipase C gamma (PLCγ) and to contribute to KSHV-induced angiogenesis. Here we investigate how the K15 protein activates the NF-κB pathway. We show that activation of NF-κB involves the recruitment of NF-κB-inducing kinase (NIK) and IKK α/β to result in the phosphorylation of p65/RelA on Ser536. A K15 mutant devoid in NIK/IKK recruitment fails to activate NF-κB but remains proficient in the stimulation of both NFAT- and AP1-dependent promoters, showing that the structural integrity of the mutant K15 protein has not been altered dramatically. Direct recruitment of NIK represents a novel way for a viral protein to activate and manipulate the NF-κB pathway. IMPORTANCE: KSHV K15 is a viral protein involved in the activation of proinflammatory and angiogenic pathways. Previous studies reported that K15 can activate the NF-κB pathway. Here we show the molecular mechanism underlying the activation of this signaling pathway by K15, which involves direct recruitment of the NF-κB-inducing kinase NIK to K15 as well as NIK-mediated NF-κB p65 phosphorylation on Ser536. K15 is the first viral protein shown to activate NF-κB through direct recruitment of NIK. These results indicate a new mechanism whereby a viral protein can manipulate the NF-κB pathway.
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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.