ArticlePLoS pathogens2014
HTLV-1 tax stabilizes MCL-1 via TRAF6-dependent K63-linked polyubiquitination to promote cell survival and transformation.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 66 citations in OpenAlex.
- Nedd4L-mediated stabilization of morphogenetic protein receptor 2 in lung fibroblasts confers protection against pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- Rewiring of the Apoptotic Rheostat in HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma.Cancers · 2026Review
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- Adult T-cell leukemia/lymphoma: molecular pathogenesis, emerging therapies, and future directions.Frontiers in oncology · 2026Review
- Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy.The FEBS journal · 2026Review
- BCL-2 family dysregulation in HTLV-1 and BLV pathogenesis and its implications for leukemogenesis and therapy.Molecular biology reports · 2025Review
- Review
- The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.Journal of virology · 2024Article
- HTLV-1 Tax Tug-of-War: Cellular Senescence and Death or Cellular Transformation.Pathogens (Basel, Switzerland) · 2024Review
- Mcl-1 Protein and Viral Infections: A Narrative Review.International journal of molecular sciences · 2024Review
- PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation.Frontiers in immunology · 2024Article
- The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8Cellular & molecular immunology · 2023Article
- TRAF6 regulates autophagy and apoptosis of melanoma cells through c-Jun/ATG16L2 signaling pathway.MedComm · 2023Article
- Shikonin Induces ROS-Dependent Apoptosis Via Mitochondria Depolarization and ER Stress in Adult T Cell Leukemia/Lymphoma.Antioxidants (Basel, Switzerland) · 2023Article
- TRAF6 autophagic degradation byAutophagy · 2022Article
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
- Co-Infection and Cancer: Host-Pathogen Interaction between Dendritic Cells and HIV-1, HTLV-1, and Other Oncogenic Viruses.Viruses · 2022Review
- UBE2B promotes ovarian cancer growth via promoting RAD18 mediated ZMYM2 monoubiquitination and stabilization.Bioengineered · 2022Article
- Regulation of HTLV-1 transformation.Bioscience reports · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
The human T-cell leukemia virus type 1 (HTLV-1) Tax protein hijacks the host ubiquitin machinery to activate IκB kinases (IKKs) and NF-κB and promote cell survival; however, the key ubiquitinated factors downstream of Tax involved in cell transformation are unknown. Using mass spectrometry, we undertook an unbiased proteome-wide quantitative survey of cellular proteins modified by ubiquitin in the presence of Tax or a Tax mutant impaired in IKK activation. Tax induced the ubiquitination of 22 cellular proteins, including the anti-apoptotic BCL-2 family member MCL-1, in an IKK-dependent manner. Tax was found to promote the nondegradative lysine 63 (K63)-linked polyubiquitination of MCL-1 that was dependent on the E3 ubiquitin ligase TRAF6 and the IKK complex. Tax interacted with and activated TRAF6, and triggered its mitochondrial localization, where it conjugated four carboxyl-terminal lysine residues of MCL-1 with K63-linked polyubiquitin chains, which stabilized and protected MCL-1 from genotoxic stress-induced degradation. TRAF6 and MCL-1 played essential roles in the survival of HTLV-1 transformed cells and the immortalization of primary T cells by HTLV-1. Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation.
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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.