ArticlePLoS pathogens2020
The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-κB activation.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Ubiquitination of LMP-1 by UFD-2 regulates apoptotic cell clearance.Cell death and differentiation · 2026Article
- Negative feedback regulation of STING signaling by TAX1BP1-directed Golgiphagy.Nature communications · 2026Article
- STARD4 suppresses tumorigenesis and attenuates enzalutamide resistance via lipid metabolic reprogramming and AR stabilization in prostate cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- REDD1 expression in podocytes facilitates renal inflammation and pyroptosis in streptozotocin-induced diabetic nephropathy.Cell death & disease · 2025Article
- The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein.Nature communications · 2024Article
- Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.Cell death & disease · 2024Review
- PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation.Frontiers in immunology · 2024Article
- Novel approaches for HTLV-1 therapy: innovative applications of CRISPR-Cas9.Revista do Instituto de Medicina Tropical de Sao Paulo · 2024Review
- Fire Burn and Cauldron Bubble: What Is in Your Genome Editing Brew?Biochemistry · 2023Review
- 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
- Mechanisms of Innate Immune Sensing of HTLV-1 and Viral Immune Evasion.Pathogens (Basel, Switzerland) · 2023Review
- HTLV-1 p12 modulates the levels of prion protein (PrPFrontiers in microbiology · 2023Article
- SF3B4 Depletion Retards the Growth of A549 Non-Small Cell Lung Cancer Cells via UBE4B-Mediated Regulation of p53/p21 and p27 Expression.Molecules and cells · 2022Article
- Harnessing the ubiquitin code to respond to environmental cues.Essays in biochemistry · 2022Article
- Enrichment of Newly Synthesized Proteins following treatment of C2C12 Myotubes with Endotoxin and Interferon-γ.Inflammation · 2022Article
- Transcription factor dynamics in plants: Insights and technologies for in vivo imaging.Plant physiology · 2022Review
- HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models.International journal of molecular sciences · 2021Review
- UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation.Nature communications · 2021Article
- Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers.Cancers · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), and the neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax protein persistently activates the NF-κB pathway to enhance the proliferation and survival of HTLV-1 infected T cells. Lysine 63 (K63)-linked polyubiquitination of Tax provides an important regulatory mechanism that promotes Tax-mediated interaction with the IKK complex and activation of NF-κB; however, the host proteins regulating Tax ubiquitination are largely unknown. To identify new Tax interacting proteins that may regulate its ubiquitination we conducted a yeast two-hybrid screen using Tax as bait. This screen yielded the E3/E4 ubiquitin conjugation factor UBE4B as a novel binding partner for Tax. Here, we confirmed the interaction between Tax and UBE4B in mammalian cells by co-immunoprecipitation assays and demonstrated colocalization by proximity ligation assay and confocal microscopy. Overexpression of UBE4B specifically enhanced Tax-induced NF-κB activation, whereas knockdown of UBE4B impaired Tax-induced NF-κB activation and the induction of NF-κB target genes in T cells and ATLL cell lines. Furthermore, depletion of UBE4B with shRNA resulted in apoptotic cell death and diminished the proliferation of ATLL cell lines. Finally, overexpression of UBE4B enhanced Tax polyubiquitination, and knockdown or CRISPR/Cas9-mediated knockout of UBE4B attenuated both K48- and K63-linked polyubiquitination of Tax. Collectively, these results implicate UBE4B in HTLV-1 Tax polyubiquitination and downstream NF-κB activation.
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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.