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PDX1, a cellular homeoprotein, binds to and regulates the activity of human cytomegalovirus immediate early promoter.

Chao, Sheng Hao and Harada, Josephine and Hyndman, Francie and Gao, Xiaoqi and Nelson, Christian and Chanda, Sumit and Caldwell, Jeremy (2004) PDX1, a cellular homeoprotein, binds to and regulates the activity of human cytomegalovirus immediate early promoter. The Journal of Biological Chemistry, 279 (16). pp. 16111-16120. ISSN 0021-9258

Abstract

Cellular homeoproteins have been shown to regulate the transcription of several viruses, including herpes simplex viruses, human papillomaviruses, and mouse mammary tumor viruses. Previous studies investigating the anti-viral mechanisms of several cyclin-dependent kinase inhibitors showed that the homeoproteins, pre B-cell leukemia transcription factor 1 (PBX1) and PBX-regulating protein-1 (PREP1), function as transcriptional activators of Moloney murine leukemia virus. Here, we examined the involvement of cellular homeoproteins in regulating the activity of the human cytomegalovirus immediate early (CMV IE) promoter. We identified a 45-bp element located at position -593 to -549 upstream of the transcription start site of the CMV IE gene, which contains multiple putative homeoprotein binding motifs. Gel shift assays demonstrated the physical association between a homeodomain protein, pancreatic-duodenal homeobox factor-1 (PDX1) and the 45-bp cytomegalovirus (CMV) region. We further determined that PDX1 represses the CMV IE promoter activity in 293 cells. Overexpression of PDX1 resulted in a decrease in transcription of the CMV IE gene. Conversely, blocking PDX1 protein synthesis and mutating the PDX1 binding sites enhanced CMV IE-dependent transcription. Collectively, our results represent the first work demonstrating that a cellular homeoprotein, PDX1, may be a repressor involved in regulation of human CMV gene expression.

Item Type: Article
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Additional Information: free final full text version available at publisher's official URL; author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
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Date Deposited: 14 Dec 2009 14:02
Last Modified: 31 Jan 2013 01:21
URI: https://oak.novartis.com/id/eprint/286

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