title: Human T-cell leukemia virus type 1 Tax relieves repression of proliferating cell nuclear antigen gene expression.
abstract: 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.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, MS-385, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Dustin C
authors.initials: DC
authors.lastname: Edwards
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Marriott
mesh_terms: D002460:Cell Line; D004260:DNA Repair; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015533:Transcriptional Activation
chemical_list: D016356:Gene Products, tax; D018809:Proliferating Cell Nuclear Antigen; C514970:tax protein, Human T-lymphotrophic virus 1
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