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Blood, 15 September 2007, Vol. 110, No. 6, pp. 2110-2120. Prepublished online as a Blood First Edition Paper on May 31, 2007; DOI 10.1182/blood-2006-11-058388. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-058388v1 110/6/2110    most recent Alert me when this article is cited Alert me if a correction is posted 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 Cheng, J. Articles by Marasco, W. A. Search for Related Content PubMed PubMed Citation Articles by Cheng, J. Articles by Marasco, W. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 28, 2006 Accepted May 17, 2007 Negative regulation of the SH2-homology-containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 tax oncoprotein Jihua Cheng, Andre R. Kydd, Koichi Nakase, Kristin M. Noonan, Akikazu Murakami, Hong Tao, Markryan Dwyer, Chen Xu, Quan Zhu, and Wayne A. Marasco* Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA, United States Department of Medicine, Harvard Medical School, Boston, MA, United States * Corresponding author; email: wayne_marasco{at}dfci.harvard.edu. Expression of SH2-Homology-Containing Protein-Tyrosine Phosphatase-1 (SHP-1), a candidate tumor suppressor, is repressed in HTLV-1 transformed lymphocyte cell lines, Adult T-cell Leukemia (ATL) cells and in other hematological malignancies. However, the mechanisms underlying regulation and repression of SHP-1 remain unclear. Herein, we cloned the putative full-length, hematopoietic cell specific SHP-1 P2 promoter and identified the "core" promoter regions. HTLV-1 Tax profoundly represses P2 promoter activity and histone deacetylase-1 (HDAC1) potentiates such inhibition. NF-B was implicated as both a rate-limiting factor for basal P2 promoter activity and important for Tax-induced Promoter Silencing (TIPS). Chromatin Immunoprecipitation studies demonstrated that NF-B dissociates from the SHP-1 P2 promoter following the binding of Tax and HDAC1. This is in agreement with co-immunoprecipitation study where NF-B competed with HDAC1 for association with Tax protein. We propose that in TIPS, Tax recruits HDAC1 to the SHP-1 P2 promoter and forms an inhibitory complex that results in deacetylation and dissociation of NF-B from the promoter and attenuation of SHP-1 expression. TIPS provides a possible first step toward HTLV-1 leukemogenesis through its down modulation of this key immediate early negative regulator of IL-2 signaling. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Nakase, J. Cheng, Q. Zhu, and W. A. Marasco Mechanisms of SHP-1 P2 promoter regulation in hematopoietic cells and its silencing in HTLV-1-transformed T cells J. Leukoc. Biol., January 1, 2009; 85(1): 165 - 174. [Abstract] [Full Text] [PDF]

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