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Cooperation between the human T-cell leukemia virus type-1 p30(II) protein and host cellular factors during oncogenic transformation and retroviral carcinogenesis

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Retrovirology201411 (Suppl 1) :P95

https://doi.org/10.1186/1742-4690-11-S1-P95

  • Published:

Keywords

  • Cellular Gene Expression
  • Leukemic Lymphocyte
  • High Intracellular Level
  • Host Cellular Factor
  • Proviral Gene

The human T-cell leukemia virus type-1 (HTLV-1) pX-encoded accessory factors, p30II and Hbz, suppress proviral gene expression and help to maintain latency as a prerequisite for the development of adult T-cell leukemia/lymphoma (ATLL). Our laboratory is studying how these viral proteins influence host cellular gene expression and signaling which may contribute to hematological disease progression. There are five clinically-defined stages of HTLV-1-associated disease (pre-ATLL, smoldering T-cell leukemia, chronic T-cell leukemia, acute T-cell leukemia, and non-Hodgkin’s T-cell lymphoma) and the transitional molecular events which lead to acute/lymphoma-stage disease are not well understood. We have previously shown that p30II interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transactivation and oncogenic potential by stabilizing recruitment of the TIP60 acetyltransferase to p30II/c-MYC/TIP60 transcription complexes. We now extend these findings by demonstrating that p30II induces acetylation of the c-MYC protein. Acetylation-defective Lys --> Arg substitution mutants of c-MYC (R5, K323R/K417R) are impaired for oncogenic foci-formation by p30II/c-MYC. Acute/lymphoma-stage ATLL clinical isolates frequently exhibit overexpression of c-MYC, due to 8q24 chromosomal translocations and/or c-myc gene amplification, and the HTLV-1-transformed T-cell-lines HuT-102 and MJG11 display significant acetylation of c-MYC. The p 53 tumor suppressor is a downstream target of c-MYC and, coincidentally, most ATLL leukemic lymphocytes contain high intracellular levels of wildtype p53. Our recent studies demonstrate that p30II activates p53 and induces the expression of p53-dependent anti-apoptotic genes which could promote oncogene-activation and contribute to ATLL tumorigenesis. These findings as well as a novel role for p30II in the long-term proliferation of lentiviral-p30II-transduced primary human T-lymphocytes will be discussed.

Authors’ Affiliations

(1)
Laboratory of Molecular Virology, Department of Biological Sciences and the Dedman College Center for Drug Discovery, Design & Delivery, Southern Methodist University, Dallas, Texas, USA

Copyright

© Romeo et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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