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A human T-cell lymphotropic virus type 1 enhancer of Myc transforming potential stabilizes Myc-TIP60 transcriptional interactions

Lookup NU author(s): Dr Luke GaughanORCiD, Professor Craig RobsonORCiD

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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 p30 II 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. Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Publication metadata

Author(s): Awasthi, S, Sharma, A, Wong, K, Zhang, J, Matlock, E, Rogers, L, Motloch, P, Takemoto, S, Taguchi, H, Cole, MD, Lüscher, B, Dittrich, O, Tagami, H, Nakatani, Y, McGee, M, Girard, AM, Gaughan, L, Robson, CN, Monnat, RJ, Harrod, R

Publication type: Article

Publication status: Published

Journal: Molecular and Cellular Biology

Year: 2005

Volume: 25

Issue: 14

Pages: 6178-6198

Print publication date: 01/07/2005

ISSN (print): 0270-7306

ISSN (electronic): 1067-8824

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/MCB.25.14.6178-6198.2005

DOI: 10.1128/MCB.25.14.6178-6198.2005

PubMed id: 15988028

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