This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Awasthi, S.
Right arrow Articles by Harrod, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Awasthi, S.
Right arrow Articles by Harrod, R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2005, p. 6178-6198, Vol. 25, No. 14
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.14.6178-6198.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Human T-Cell Lymphotropic Virus Type 1 Enhancer of Myc Transforming Potential Stabilizes Myc-TIP60 Transcriptional Interactions

Soumya Awasthi,1 Anima Sharma,1 Kasuen Wong,1 Junyu Zhang,1 Elizabeth F. Matlock,1 Lowery Rogers,1 Pamela Motloch,1 Shigeki Takemoto,2 Hirokuni Taguchi,2 Michael D. Cole,3 Bernhard Lüscher,4 Oliver Dittrich,4,{dagger} Hideaki Tagami,5 Yoshihiro Nakatani,5 Monnie McGee,6 Anne-Marie Girard,7 Luke Gaughan,8 Craig N. Robson,8 Raymond J. Monnat Jr.,9 and Robert Harrod1*

Laboratory of Molecular Virology, Department of Biological Sciences, Southern Methodist University, 334-DLS, 6501 Airline Drive, Dallas, Texas 75275-0376,1 Department of Hematology and Respiratory Medicine, Kochi Medical School Hospital, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan,2 Department of Pharmacology and Toxicology, Dartmouth University Medical School and the Norris Cotton Cancer Center, Hanover, New Hampshire 03755,3 Abt. Biochemie und Molekularbiologie, Institute für Biochemie, Klinikum der RWTH, Pauwelssttrasse 30, 52057 Aachen, Germany,4 Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115,5 Department of Statistical Science, Southern Methodist University, 3225 Daniels Avenue, Dallas, Texas 75275-0332,6 Center for Gene Research and Biotechnology, Oregon State University, Corvallis, Oregon 97331,7 School of Surgical Sciences, University of Newcastle upon Tyne Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom,8 Department of Pathology, University of Washington, Box 357705, Seattle, Washington 98195-77059

Received 10 January 2005/ Returned for modification 17 February 2005/ Accepted 6 April 2005

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.

* Corresponding author. Mailing address: Laboratory of Molecular Virology, Department of Biological Sciences, Southern Methodist University, 334-DLS, 6501 Airline Drive, Dallas, TX 75275-0376. Phone: (214) 768-3864. Fax: (214) 768-3955. E-mail: rharrod{at}mail.smu.edu.

{dagger} Present address: Medizinische Hochschule Hannover, Institut für Pharmakologie, 30625 Hannover, Germany.

Molecular and Cellular Biology, July 2005, p. 6178-6198, Vol. 25, No. 14
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.14.6178-6198.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Li, M., Kesic, M., Yin, H., Yu, L., Green, P. L. (2009). Kinetic Analysis of Human T-Cell Leukemia Virus Type 1 Gene Expression in Cell Culture and Infected Animals. J. Virol. 83: 3788-3797 [Abstract] [Full Text]  
  • Yeung, M. L., Yasunaga, J.-i., Bennasser, Y., Dusetti, N., Harris, D., Ahmad, N., Matsuoka, M., Jeang, K.-T. (2008). Roles for MicroRNAs, miR-93 and miR-130b, and Tumor Protein 53-Induced Nuclear Protein 1 Tumor Suppressor in Cell Growth Dysregulation by Human T-Cell Lymphotrophic Virus 1. Cancer Res. 68: 8976-8985 [Abstract] [Full Text]  
  • Ben-Israel, H., Sharf, R., Rechavi, G., Kleinberger, T. (2008). Adenovirus E4orf4 Protein Downregulates MYC Expression through Interaction with the PP2A-B55 Subunit. J. Virol. 82: 9381-9388 [Abstract] [Full Text]  
  • Hiraragi, H., Kim, S.-J., Phipps, A. J., Silic-Benussi, M., Ciminale, V., Ratner, L., Green, P. L., Lairmore, M. D. (2006). Human T-Lymphotropic Virus Type 1 Mitochondrion-Localizing Protein p13II Is Required for Viral Infectivity In Vivo.. J. Virol. 80: 3469-3476 [Abstract] [Full Text]  
  • Younis, I., Boris-Lawrie, K., Green, P. L. (2006). Human T-Cell Leukemia Virus Open Reading Frame II Encodes a Posttranscriptional Repressor That Is Recruited at the Level of Transcription. J. Virol. 80: 181-191 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»