ArticleMolecular and cellular biology2014
p53 tumor suppressor protein stability and transcriptional activity are targeted by Kaposi's sarcoma-associated herpesvirus-encoded viral interferon regulatory factor 3.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy.Virulence · 2025Review
- Correlation of p53 oligomeric status and its subcellular localization in the presence of the AML-associated NPM mutant.PloS one · 2025Article
- Nucleo-cytoplasmic environment modulates spatiotemporal p53 phase separation.Science advances · 2024Article
- Review
- Molecular Mechanisms of Kaposi Sarcoma-Associated Herpesvirus (HHV8)-Related Lymphomagenesis.Cancers · 2024Review
- Review
- Review
- Adaptive homeostasis and the p53 isoform network.EMBO reports · 2021Review
- The ORF45 Protein of Kaposi Sarcoma-Associated Herpesvirus Is an Inhibitor of p53 Signaling during Viral Reactivation.Journal of virology · 2021Article
- Metabolic Control by DNA Tumor Virus-Encoded Proteins.Pathogens (Basel, Switzerland) · 2021Review
- Proximity Biotin Labeling Reveals Kaposi's Sarcoma-Associated Herpesvirus Interferon Regulatory Factor Networks.Journal of virology · 2021Article
- Identify specific gene pairs for subarachnoid hemorrhage based on wavelet analysis and genetic algorithm.PloS one · 2021Article
- KSHV requires vCyclin to overcome replicative senescence in primary human lymphatic endothelial cells.PLoS pathogens · 2020Article
- MXD3 antisense oligonucleotide with superparamagnetic iron oxide nanoparticles: A new targeted approach for neuroblastoma.Nanomedicine : nanotechnology, biology, and medicine · 2020Article
- USP7-Dependent Regulation of TRAF Activation and Signaling by a Viral Interferon Regulatory Factor Homologue.Journal of virology · 2020Article
- Trisenox Disrupts MDM2-DAXX-HAUSP Complex and Induces Apoptosis in a Mouse Model of Acute Leukemia.Journal of Cancer · 2020Article
- p53 Phosphomimetics Preserve Transient Secondary Structure but Reduce Binding to Mdm2 and MdmX.Biomolecules · 2019Article
- Human Oncoviruses and p53 Tumor Suppressor Pathway Deregulation at the Origin of Human Cancers.Cancers · 2018Review
- Human Herpesvirus 8 Interferon Regulatory Factors 1 and 3 Mediate Replication and Latency Activities via Interactions with USP7 Deubiquitinase.Journal of virology · 2018Article
- MDM2 gene polymorphisms and risk of classic Kaposi's sarcoma among Iranian patients.Medical microbiology and immunology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viruses have developed numerous strategies to counteract the host cell defense. Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA tumor virus linked to the development of Kaposi's sarcoma, Castleman's disease, and primary effusion lymphoma (PEL). The virus-encoded viral interferon regulatory factor 3 (vIRF-3) gene is a latent gene which is involved in the regulation of apoptosis, cell cycle, antiviral immunity, and tumorigenesis. vIRF-3 was shown to interact with p53 and inhibit p53-mediated apoptosis. However, the molecular mechanism underlying this phenomenon has not been established. Here, we show that vIRF-3 associates with the DNA-binding domain of p53, inhibits p53 phosphorylation on serine residues S15 and S20, and antagonizes p53 oligomerization and the DNA-binding affinity. Furthermore, vIRF-3 destabilizes p53 protein by increasing the levels of p53 polyubiquitination and targeting p53 for proteasome-mediated degradation. Consequently, vIRF-3 attenuates p53-mediated transcription of the growth-regulatory p21 gene. These effects of vIRF-3 are of biological relevance since the knockdown of vIRF-3 expression in KSHV-positive BC-3 cells, derived from PEL, leads to an increase in p53 phosphorylation, enhancement of p53 stability, and activation of p21 gene transcription. Collectively, these data suggest that KSHV evolved an efficient mechanism to downregulate p53 function and thus facilitate uncontrolled cell proliferation and tumor growth.
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