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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1490-1497. Prepublished online as a Blood First Edition Paper on May 20, 2004; DOI 10.1182/blood-2003-12-4174. This Article Full Text Full Text (PDF) Erratum (v109,p411) All Versions of this Article: 2003-12-4174v1 104/5/1490    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jeong, S.-J. Articles by Pise-Masison, C. A. Search for Related Content PubMed PubMed Citation Articles by Jeong, S.-J. Articles by Pise-Masison, C. A. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA HTLV-I Tax induces a novel interaction between p65/RelA and p53 that results in inhibition of p53 transcriptional activity Soo-Jin Jeong, Michael Radonovich, John N. Brady, and Cynthia A. Pise-Masison From the Virus Tumor Biology Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. Nuclear factor B (NF-B) activation plays a critical role in oncogenesis by human T-cell lymphotrophic virus type I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL), and is indispensable for maintenance of the malignant phenotype. In T lymphocytes, Tax-mediated p53 inhibition is dependent on Tax activation of the NF-B pathway and is linked to p53 phosphorylation. We now report that blocking NF-B transcriptional activation in HTLV-I–transformed cells restores p53 activity. Further, using mouse embryo fibroblast (MEF) null cells and antisense oligonucleotides to inhibit expression of NF-B family members, we demonstrate that the p65 subunit of NF-B is uniquely involved in p53 inhibition. Coimmunoprecipitation assays demonstrate an interaction between p65 and p53 in HTLV-I–transformed cells. In transient transfection assays, we demonstrate that Tax induces the p53-p65 interaction. Phosphorylation of p53 at serines 15 and 392 is critical for complex formation. Importantly, Tax-mediated p53 inhibition correlates with p65 and p53 interaction. By using chromatin immunoprecipitation (ChIP) assays, we find that in HTLV-I–transformed cells p53 and p65 form a complex on the inactive, p53-responsive murine double minute 2 (MDM2) promoter. Consistent with reduced transcriptional activity, transcription factor IID (TFIID) binding is not observed. 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