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Cited by 156T-cell and Retrovirus StudiesViral-associated cancers and disordersNF-κB Signaling Pathways

HTLV Tax: A Fascinating Multifunctional Co-Regulator of Viral and Cellular Pathways

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Currer, Robert, Van Duyne, Rachel, Jaworski, Elizabeth, Guendel, Irene, Sampey, Gavin, Das, Ravi, Narayanan, Aarthi, Kashanchi, Fatah·2012·Frontiers in Microbiology
DOI 10.3389/fmicb.2012.00406PMC PMC3510432
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Abstract

Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2-5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent body of literature that refines our understanding of cellular transformation. A focused range of topics are discussed in this review including Tax-mediated regulation of the viral promoter and other cellular pathways, particularly the connection of the NF-κB pathway to both post-translational modifications (PTMs) of Tax and subcellular localization. Specifically, recent research on polyubiquitination of Tax as it relates to the activation of the IkappaB kinase (IKK) complex is highlighted. Regulation of the cell cycle and DNA damage responses due to Tax are also discussed, including Tax interaction with minichromosome maintenance proteins and the role of Tax in chromatin remodeling. The recent identification of HTLV-3 has amplified the importance of the characterization of emerging viral pathogens. The challenge of the molecular determination of pathogenicity and malignant disease of this virus lies in the comparison of the viral transactivators of HTLV-1, -2, and -3 in terms of transformation and immortalization. Consequently, differences between the three proteins are currently being studied to determine what factors are required for the differences in tumorogenesis.

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  • Tax plays a central role in cell-to-cell transmission of HTLV-1 across VS, can be found in conduits, is not incorporated into viral particles, affects signaling pathways including NF-kB, and can sensitize recipient cells to HTLV-1 infection.

    “The HTLV-1 regulatory protein, Tax, which, in producer cells, plays a central role in the cell-to-cell transmission of HTLV-1 across VS, can also be found in conduits. Tax is not incorporated into viral particles, but affects many signaling pathways, including NF-kB [119], and can also induce changes in recipient cells, sensitizing them to HTLV-1 infection [120].”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [119]

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Authors
Currer, R., Van Duyne, R., Jaworski, E., Guendel, I., Sampey, G., Das, R., Narayanan, A., & Kashanchi, F.
Affiliations
George Mason University (US)
Corresponding author
Kashanchi, Fatah
ORCID
Venue
Frontiers in Microbiology
Publisher
Frontiers Media SA
Published
2012
Volume
3
Pages
406-406
ISSN
1664-302X (ISSN-L)
DOI
10.3389/fmicb.2012.00406
PMC
PMC3510432
OpenAlex
W2159407168
Cited by
156
References
3
Citations by year
2026: 6 · 2025: 6 · 2024: 14 · 2023: 9 · 2022: 12 · 2021: 10 · 2020: 16 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 14 · 2015: 14 · 2014: 10 · 2013: 9 · 2012: 1
FWCI
4.76
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Microbiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
HTLV-1, Tax oncoprotein, adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis, viral transactivator, carcinogenesis, NF-κB signaling, polyubiquitination, IκB kinase complex, post-translational modification, minichromosome maintenance proteins, cell cycle regulation, DNA damage response, chromatin remodeling, HTLV-III, cell transformation, cell immortalization

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