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A Human T-Cell Lymphotropic Virus Type 1 Enhancer of Myc Transforming Potential Stabilizes Myc- TIP60 Transcriptional Interactions
Molecular and Cellular Biology (2005)
  • S. Awasthi, Southern Methodist University
  • A. Sharma, Southern Methodist University
  • Kasuen Wong, Southern Methodist University
  • J. Zhang, Southern Methodist University
  • E. F. Matlock, Southern Methodist University
  • L. Rogers, Southern Methodist University
  • P. Motloch, Southern Methodist University
  • S. Takemoto
  • H. Taguchi
  • M. D. Cole

The human T-cell lymphotropic virus type 1 (HTLV-1) infects and transforms CD4+ lymphocytes and causes adult T-cell leukemia/lymphoma (ATLL), an aggressive lymphoproliferative disease that is often fatal. Here, we demonstrate that the HTLV-1 pX splice-variant p30II markedly enhances the transforming potential of Myc and transcriptionally activates the human cyclin D2 promoter, dependent upon its conserved Myc-responsive E-box enhancer elements, which are associated with increased S-phase entry and multinucleation. Enhancement of c-Myc transforming activity by HTLV-1 p30II is dependent upon the transcriptional coactivators, transforming transcriptional activator protein/p434 and TIP60, and it requires TIP60 histone acetyltransferase (HAT) activity and correlates with the stabilization of HTLV-1 p30II/Myc-TIP60 chromatin-remodeling complexes. The p30II oncoprotein colocalizes and coimmunoprecipitates with Myc-TIP60 complexes in cultured HTLV-1-infected ATLL patient lymphocytes. Amino acid residues 99 to 154 within HTLV-1 p30II interact with the TIP60 HAT, and p30II transcriptionally activates numerous cellular genes in a TIP60-dependent or TIP60-independent manner, as determined by microarray gene expression analyses. Importantly, these results suggest that p30II functions as a novel retroviral modulator of Myc-TIP60-transforming interactions that may contribute to adult T-cell leukemogenesis.

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S. Awasthi, A. Sharma, Kasuen Wong, J. Zhang, et al.. "A Human T-Cell Lymphotropic Virus Type 1 Enhancer of Myc Transforming Potential Stabilizes Myc- TIP60 Transcriptional Interactions" Molecular and Cellular Biology Vol. 25 Iss. 14 (2005)
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