ArticlePLoS pathogens2011
NF-κB hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 127 citations in OpenAlex.
- Spontaneous lymphoproliferation differentiates two groups of HTLV-1 asymptomatic carriers: with and without high cell proliferation and death.Immunologic research · 2026Article
- Rewiring of the Apoptotic Rheostat in HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma.Cancers · 2026Review
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- Recent advances in infections as risk factors for lymphoma: a review of the effects of viral, bacterial, and fungal infections in lymphoma.Archives of microbiology · 2025Review
- Viral oncogenes drive biphenotypic lymphoproliferative malignancy in transgenic mice.Scientific reports · 2025Article
- Review
- Role of the CTCF binding site in Human T-Cell Leukemia Virus-1 pathogenesis.PLoS pathogens · 2025Article
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- Activation of theGenes · 2024Article
- The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.Journal of virology · 2024Article
- Trans-Activation of theGenes · 2024Article
- Establishment of a novel human T-cell leukemia virus type 1 infection model using cell-free virus.Journal of virology · 2024Article
- Article
- HTLV-1 Tax Tug-of-War: Cellular Senescence and Death or Cellular Transformation.Pathogens (Basel, Switzerland) · 2024Review
- Human T-Cell Leukemia Virus Type 1 Oncogenesis between Active Expression and Latency: A Possible Source for the Development of Therapeutic Targets.International journal of molecular sciences · 2023Review
- The Pleiotropic Effects of YBX1 on HTLV-1 Transcription.International journal of molecular sciences · 2023Article
- Mechanisms of Innate Immune Sensing of HTLV-1 and Viral Immune Evasion.Pathogens (Basel, Switzerland) · 2023Review
- Origin and functional role of antisense transcription in endogenous and exogenous retroviruses.Retrovirology · 2023Review
- Article
- Primary cells from patients with adult T cell leukemia/lymphoma depend on HTLV-1 Tax expression for NF-κB activation and survival.Blood cancer journal · 2023Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of I-κB kinases (IKKs) and NF-κB by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation. Paradoxically, expression of Tax in most cells leads to drastic up-regulation of cyclin-dependent kinase inhibitors, p21(CIP1/WAF1) and p27(KIP1), which cause p53-/pRb-independent cellular senescence. Here we demonstrate that p21(CIP1/WAF1)-/p27(KIP1)-mediated senescence constitutes a checkpoint against IKK/NF-κB hyper-activation. Senescence induced by Tax in HeLa cells is attenuated by mutations in Tax that reduce IKK/NF-κB activation and prevented by blocking NF-κB using a degradation-resistant mutant of I-κBα despite constitutive IKK activation. Small hairpin RNA-mediated knockdown indicates that RelA induces this senescence program by acting upstream of the anaphase promoting complex and RelB to stabilize p27(KIP1) protein and p21(CIP1/WAF1) mRNA respectively. Finally, we show that down-regulation of NF-κB by the HTLV-1 anti-sense protein, HBZ, delay or prevent the onset of Tax-induced senescence. We propose that the balance between Tax and HBZ expression determines the outcome of HTLV-1 infection. Robust HTLV-1 replication and elevated Tax expression drive IKK/NF-κB hyper-activation and trigger senescence. HBZ, however, modulates Tax-mediated viral replication and NF-κB activation, thus allowing HTLV-1-infected cells to proliferate, persist, and evolve. Finally, inactivation of the senescence checkpoint can facilitate persistent NF-κB activation and leukemogenesis.
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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.