| Literature DB >> 15988028 |
Soumya Awasthi1, Anima Sharma, Kasuen Wong, Junyu Zhang, Elizabeth F Matlock, Lowery Rogers, Pamela Motloch, Shigeki Takemoto, Hirokuni Taguchi, Michael D Cole, Bernhard Lüscher, Oliver Dittrich, Hideaki Tagami, Yoshihiro Nakatani, Monnie McGee, Anne-Marie Girard, Luke Gaughan, Craig N Robson, Raymond J Monnat, Robert Harrod.
Abstract
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.Entities:
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Year: 2005 PMID： 15988028 PMCID： PMC1168837 DOI： 10.1128/MCB.25.14.6178-6198.2005
Source DB: PubMed Journal: Mol Cell Biol ISSN： 0270-7306 Impact factor: 4.272