ArticlePLoS pathogens2017
HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 38 citations in OpenAlex.
- Listeria promotes systemic infection by targeting the host deubiquitinase CYLD.Nature communications · 2026Article
- Review
- A novel ubiquitination-based molecular signature predicts prognosis in diffuse large B-cell lymphoma.Annals of hematology · 2025Article
- Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges.Viruses · 2025Review
- Deciphering Key Regulatory Roles of Linear Ubiquitination in Cell Fate Determination and Disease.Research (Washington, D.C.) · 2025Review
- TRAF7 determines circadian period through ubiquitination and degradation of DBP.Communications biology · 2024Article
- Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection.Nature communications · 2024Article
- PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation.Frontiers in immunology · 2024Article
- The helicase-like transcription factor redirects the autophagic flux and restricts human T cell leukemia virus type 1 infection.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Viral, genetic, and immune factors in the oncogenesis of adult T-cell leukemia/lymphoma.International journal of hematology · 2023Review
- NF-κB-Induced R-Loops and Genomic Instability in HTLV-1-Infected and Adult T-Cell Leukemia Cells.Viruses · 2022Review
- New Look of EBV LMP1 Signaling Landscape.Cancers · 2021Review
- NF-κB-induced R-loop accumulation and DNA damage select for nucleotide excision repair deficiencies in adult T cell leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Met1-linked ubiquitin signalling in health and disease: inflammation, immunity, cancer, and beyond.Cell death and differentiation · 2021Review
- The Met1-linked ubiquitin machinery in inflammation and infection.Cell death and differentiation · 2021Review
- Review
- TNF receptor-associated factor 6 (TRAF6) plays crucial roles in multiple biological systems through polyubiquitination-mediated NF-κB activation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2021Review
- The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-κB activation.PLoS pathogens · 2020Article
- Mechanisms of Oncogenesis by HTLV-1 Tax.Pathogens (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation.
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