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The TP53-Induced Glycolysis and Apoptosis Regulator mediates cooperation between HTLV-1 p30II and the retroviral oncoproteins Tax and HBZ and is highly expressed in an in vivo xenograft model of HTLV-1-induced lymphoma.

Authors
  • Hutchison, Tetiana1
  • Malu, Aditi1
  • Yapindi, Laçin1
  • Bergeson, Rachel1
  • Peck, Kendra1
  • Romeo, Megan1
  • Harrod, Carolyn1
  • Pope, Jordan1
  • Smitherman, Louisa1
  • Gwinn, Wesleigh1
  • Ratner, Lee2
  • Yates, Courtney3
  • Harrod, Robert4
  • 1 Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design & Delivery, Southern Methodist University, 6501 Airline Drive, 334-DLS, Dallas, TX 75275-0376, United States. , (United States)
  • 2 Departments of Medicine and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, United States. , (United States)
  • 3 Laboratory Animal Resource Center, Southern Methodist University, Dallas, TX 75275, United States. , (United States)
  • 4 Laboratory of Molecular Virology, Department of Biological Sciences, and The Dedman College Center for Drug Discovery, Design & Delivery, Southern Methodist University, 6501 Airline Drive, 334-DLS, Dallas, TX 75275-0376, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Virology
Publisher
Elsevier
Publication Date
May 16, 2018
Volume
520
Pages
39–58
Identifiers
DOI: 10.1016/j.virol.2018.05.007
PMID: 29777913
Source
Medline
Keywords
License
Unknown

Abstract

The human T-cell leukemia virus type-1 (HTLV-1) is an oncoretrovirus that infects and transforms CD4+ T-cells and causes adult T-cell leukemia/lymphoma (ATLL) -an aggressive lymphoproliferative disease that is highly refractive to most anticancer therapies. The HTLV-1 proviral genome encodes several regulatory products within a conserved 3' nucleotide sequence, known as pX; however, it remains unclear how these factors might cooperate or dynamically interact in virus-infected cells. Here we demonstrate that the HTLV-1 latency-maintenance factor p30II induces the TP53-induced glycolysis and apoptosis regulator (TIGAR) and counters the oxidative stress, mitochondrial damage, and cytotoxicity caused by the viral oncoproteins Tax and HBZ. The p30II protein cooperates with Tax and HBZ and enhances their oncogenic potential in colony transformation/foci-formation assays. Further, we have shown that TIGAR is highly expressed in HTLV-1-induced tumors associated with oncogene dysregulation and increased angiogenesis in an in vivo xenograft model of HTLV-1-induced T-cell lymphoma. These findings provide the first evidence that p30II likely collaborates as an ancillary factor for the major oncoproteins Tax and HBZ during retroviral carcinogenesis.

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