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Journal of Virology, June 2007, p. 6089-6098, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02179-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human T-Cell Leukemia Virus Type 1 Tax Enhances Serum Response Factor DNA Binding and Alters Site Selection{triangledown}

Heather Y. Winter and Susan J. Marriott*

Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030

Received 4 October 2006/ Accepted 16 March 2007

Human T-cell leukemia virus type I (HTLV-1) is the etiological agent of adult T-cell leukemia. The viral transforming protein Tax regulates the transcription of viral and cellular genes by interacting with cellular transcription factors and coactivators. The effects of Tax on cellular gene expression have an important impact on HTLV-1-mediated cellular transformation. Expression of the c-fos cellular oncogene is regulated by serum response factor (SRF), and Tax is known to induce c-fos gene expression by activating SRF-responsive transcription. SRF activates cellular gene expression by binding to a consensus DNA sequence (CArG box) located within a serum response element (SRE). Since SRF activates transcription of many growth regulatory genes, this pathway is likely to have a significant impact on Tax-mediated transformation. Here we demonstrate that Tax interacts with SRF and enhances the binding of SRF to SREs located in the c-fos, Nur77, and viral promoters. Also, we establish that in the presence of Tax, SRF selects more divergent CArG box sequences than in the absence of Tax, revealing a novel mechanism for regulating SRF-responsive gene expression. Finally, increased association of SRF with chromatin and specific promoters was observed in Tax-expressing cells, correlating with increased c-fos and Nur77 mRNA levels in Tax-expressing cells. These results suggest that Tax activates SRF-responsive transcription by enhancing its binding affinity to multiple different SRE sequences.


* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4440. Fax: (713) 798-4435. E-mail: susanm{at}bcm.tmc.edu

{triangledown} Published ahead of print on 21 March 2007.


Journal of Virology, June 2007, p. 6089-6098, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.02179-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Edwards, D. C., Marriott, S. J. (2008). Human T-Cell Leukemia Virus Type 1 Tax Relieves Repression of Proliferating Cell Nuclear Antigen Gene Expression. J. Virol. 82: 11714-11722 [Abstract] [Full Text]  
  • Taylor, G P (2007). Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma. J. Clin. Pathol. 60: 1392-1396 [Abstract] [Full Text]