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- W2066714427 endingPage "2120" @default.
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- W2066714427 abstract "Abstract Expression of SH2-homology–containing protein-tyrosine phosphatase-1 (SHP-1), a candidate tumor suppressor, is repressed in human T-cell leukemia virus type-1 (HTLV-1)–transformed lymphocyte cell lines, adult T-cell leukemia (ATL) cells, and in other hematologic 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-κB 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-κB dissociates from the SHP-1 P2 promoter following the binding of Tax and HDAC1. This is in agreement with coimmunoprecipitation studies where NF-κB 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-κB 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." @default.
- W2066714427 created "2016-06-24" @default.
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- W2066714427 date "2007-09-15" @default.
- W2066714427 modified "2023-09-30" @default.
- W2066714427 title "Negative regulation of the SH2-homology–containing protein-tyrosine phosphatase-1 (SHP-1) P2 promoter by the HTLV-1 Tax oncoprotein" @default.
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- W2066714427 doi "https://doi.org/10.1182/blood-2006-11-058388" @default.
- W2066714427 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1976352" @default.
- W2066714427 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17540846" @default.
- W2066714427 hasPublicationYear "2007" @default.