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

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.

• Authors: Soumya Awasthi, 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 Jr, Robert Harrod
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 25 Issue 14 Pg. 6178-98 (Jul 2005) ISSN: 0270-7306 [Print] United States
• PMID: 15988028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCND2 protein, human
• Cyclin D2
• Cyclins
• MYC protein, human
• Proto-Oncogene Proteins c-myc
• Retroviridae Proteins
• tof protein, Human T-lymphotropic virus 1
• Acetyltransferases
• Histone Acetyltransferases
• KAT5 protein, human
• Lysine Acetyltransferase 5

Topics

• Acetyltransferases (analysis, metabolism)
• Alternative Splicing
• CD4-Positive T-Lymphocytes (chemistry, virology)
• Cell Transformation, Neoplastic
• Chromatin Assembly and Disassembly
• Cyclin D2
• Cyclins (genetics)
• E-Box Elements (genetics)
• Gene Expression Profiling
• Histone Acetyltransferases
• Human T-lymphotropic virus 1 (genetics, physiology)
• Humans
• Leukemia-Lymphoma, Adult T-Cell (genetics, virology)
• Lysine Acetyltransferase 5
• Oligonucleotide Array Sequence Analysis
• Promoter Regions, Genetic
• Proto-Oncogene Proteins c-myc (metabolism)
• Retroviridae Proteins (analysis, genetics, metabolism)
• Transcription, Genetic
• Transcriptional Activation