ArticleJournal of the National Cancer Institute2009
Mechanism of Fas signaling regulation by human herpesvirus 8 K1 oncoprotein.
Article in Journal of the National Cancer Institute, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Oncogenic Mechanisms of Kaposi's Sarcoma-Associated Herpesvirus on Cell Metabolism and Cell Transformation.Journal of medical virology · 2025Review
- Novel Insights into the Roles of Bcl-2 Homolog Nr-13 (vNr-13) Encoded by Herpesvirus of Turkeys in the Virus Replication Cycle, Mitochondrial Networks, and Apoptosis Inhibition.Journal of virology · 2020Article
- Review
- The KSHV K1 Protein Modulates AMPK Function to Enhance Cell Survival.PLoS pathogens · 2016Article
- Lymphoid hyperplasia and lymphoma in KSHV K1 transgenic mice.Histology and histopathology · 2015Article
- Engagement of Fas on Macrophages Modulates Poly I:C induced cytokine production with specific enhancement of IP-10.PloS one · 2015Article
- FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma.Leukemia · 2014Article
- CD74 interferes with the expression of fas receptor on the surface of lymphoma cells.Journal of experimental & clinical cancer research : CR · 2014Article
- HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway.Nucleic acids research · 2014Article
- Article
- The peptide derived from the Ig-like domain of human herpesvirus 8 K1 protein induces death in hematological cancer cells.Journal of experimental & clinical cancer research : CR · 2012Article
- Alpha-Tocopherol Alters Transcription Activities that Modulates Tumor Necrosis Factor Alpha (TNF-α) Induced Inflammatory Response in Bovine Cells.Gene regulation and systems biology · 2012Article
- PMLRARα binds to Fas and suppresses Fas-mediated apoptosis through recruiting c-FLIP in vivo.Blood · 2011Article
- Interactions between Hsp90 and oncogenic viruses: implications for viral cancer therapeutics.American journal of cancer research · 2011Article
- Kaposi's sarcoma and its associated herpesvirus.Nature reviews. Cancer · 2010Review
- Hsp90 and Hsp40/Erdj3 are required for the expression and anti-apoptotic function of KSHV K1.Oncogene · 2010Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHerpesvirus 8 (HHV-8) oncoprotein K1 is linked to lymphoproliferation and suppression of apoptosis mediated by the Fas death receptor. Expression of K1 in transgenic mice induces accumulation of lymphoid tissue cells and lymphoma.
methodsTo examine how K1 and Fas interact to suppress apoptosis, K1-Fas binding was studied in human embryonic kidney (HEK) and lymphoma (BJAB) cells that expressed wild-type K1 or a K1 Ig domain deletion mutant and were treated with Fas ligand (FasL) or an agonistic Fas antibody, using immunoprecipitation and Western blot analysis. Cleavage of caspase-3 and apoptosis was compared in liver samples from mice that were transfected with empty vector vs with plasmids expressing wild-type K1 or a K1 Ig deletion mutant and treated with agonistic Fas antibody for 7 hours. These studies used immunohistochemical staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. All statistical tests were two-sided.
resultsImmunoprecipitation and Western blot analysis of transfected HEK and BJAB cells revealed that wild-type K1 but not Ig-deleted K1 binds to Fas and prevents Fas activation by FasL or by an agonistic Fas antibody. More mice that were transfected with wild-type K1 (7 of 10) than mice transfected with empty vector (3 of 13) or the K1 Ig deletion mutant (0 of 6) survived treatment with the agonistic Fas antibody. Compared with vector-transfected mice, livers of wild-type K1-transfected mice contained fewer cells in which caspase-3 was cleaved (87.6% vs 58.0%, difference = 29.6%, 95% confidence interval [CI] = 19.2% to 40.0%; P = .003) and fewer apoptotic cells (83.7% vs 34.2%, difference = 49.5%, 95% CI = 39.8% to 59.2%; P = .003).
conclusionsK1 blocks Fas signaling by directly binding to Fas through the Ig-like domain of K1 and preventing binding of FasL. The relative resistance of cancer cells to Fas-mediated apoptosis may be due to the inhibition of Fas by Ig domain-containing proteins.
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