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The regulatory protein Tax 1 encoded by HTLV-1 plays a pivotal role in T-cell transformation by deregulating the function and expression of several cellular factors. In the present study, we examined the effect of Tax 1 on VEGF expression at transcriptional and posttranscriptional levels in order to elucidate the regulatory mechanisms involved. Using functional assays, we demonstrate that Tax 1 downregulates the VEGF promoter through a cluster of Sp1 sites located close to the transcriptional start site. Using gel mobility shift assays, we show that Tax 1 reduced Sp1:DNA complex formation. We demonstrate that the level of secreted VEGF was significantly lower in Tax 1-transfected 293T cells compared to nontransfected cells, which is consistent with the observed downregulatory effect of Tax 1 at the transcription level. We showed that VEGF was secreted by HTLV-1-transformed and nontransformed cells, irrespective of Tax 1 expression. Overall our data indicate that, contrary to a previous report, Tax 1 downregulates VEGF expression and suggest there are Tax 1-independent mechanisms of VEGF activation in ATL.<\/jats:p>","DOI":"10.1128\/jvi.02166-09","type":"journal-article","created":{"date-parts":[[2010,3,18]],"date-time":"2010-03-18T00:46:53Z","timestamp":1268873213000},"page":"5222-5228","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Tax 1-Independent Induction of Vascular Endothelial Growth Factor in Adult T-Cell Leukemia Caused by Human T-Cell Leukemia Virus Type 1"],"prefix":"10.1128","volume":"84","author":[{"given":"Karen M.","family":"Watters","sequence":"first","affiliation":[{"name":"Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Dean","sequence":"additional","affiliation":[{"name":"Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginie","family":"Gautier","sequence":"additional","affiliation":[{"name":"Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W.","family":"Hall","sequence":"additional","affiliation":[{"name":"Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noreen","family":"Sheehy","sequence":"additional","affiliation":[{"name":"Centre for Research in Infectious Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2007.02.006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-002-0507-6"},{"key":"e_1_3_2_4_2","first-page":"2281","volume":"21","year":"2001","unstructured":"Avramis, I. 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