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Journal of Virology, December 2008, p. 11714-11722, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.00356-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human T-Cell Leukemia Virus Type 1 Tax Relieves Repression of Proliferating Cell Nuclear Antigen Gene Expression{triangledown}

Dustin C. Edwards and Susan J. Marriott*

Department of Molecular Virology and Microbiology, Baylor College of Medicine, MS-385, One Baylor Plaza, Houston, Texas 77030

Received 18 February 2008/ Accepted 9 September 2008

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia. The transforming ability of Tax, the viral oncoprotein, is believed to depend on interactions with cell cycle regulators and on transactivation of genes that control cellular proliferation, including proliferating cell nuclear antigen (PCNA), a cofactor associated with DNA replication and repair. Tax associates with cellular transcription factors to alter their affinity for cognate DNA elements, leading to increased or decreased transcription from that promoter. Although it has been demonstrated that Tax transactivates the PCNA promoter, the mechanism of transcriptional activation is unknown. Here we report a cellular complex that binds specifically to a novel site within the minimal Tax-responsive element of the TATAA-less PCNA promoter. Mutation at this binding site or Tax expression inhibited complex formation and increased promoter activity, suggesting that the complex is a transcriptional repressor. The activation of PCNA gene expression by Tax and consequential decrease in nucleotide excision repair mediated by PCNA overexpression could contribute to the reduced DNA repair capacity and genomic instability observed in HTLV-1-infected cells.


* Corresponding author. Mailing address: Department of Molecular Virology and Microbiology, Baylor College of Medicine, MS-385, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4440. Fax: (713) 798-4435. E-mail: susanm{at}bcm.edu

{triangledown} Published ahead of print on 17 September 2008.


Journal of Virology, December 2008, p. 11714-11722, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.00356-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.