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Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain. | Polakowski et al. Retrovirology 2010 7 61 http www.retrovirology.eom content 7 1 61 RETROVIROLOGY RESEARCH Open Access Expression of a protein involved in bone resorption Dkk1 is activated by HTLV-1 bZIP factor through its activation domain Nicholas Polakowski 1 Heather Gregory1 Jean-Michel Mesnard2 Isabelle Lemasson1 Abstract Background Human T-cell leukemia virus type 1 HTLV-1 is the etiologic agent of adult T-cell leukemia a malignancy characterized by uncontrolled proliferation of virally-infected CD4 T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus contains a unique antisense gene that expresses HTLV-1 basic leucine zipper bZIP factor HBZ . HBZ is localized to the nucleus where it regulates levels of transcription by binding to certain cellular transcriptional regulators. Among its protein targets HBZ forms a stable complex with the homologous cellular coactivators p300 and CBP which is modulated through two N-terminal LXXLL motifs in the viral protein and the conserved KIX domain in the coactivators. Results To determine the effects of these interactions on transcription we performed a preliminary microarray analysis comparing levels of gene expression in cells with wild-type HBZ versus cells with HBZ mutated in its LXXLL motifs. DKK1 which encodes the secreted Wnt signaling inhibitor Dickkopf-1 Dkk1 was confirmed to be transcriptionally activated by HBZ but not its mutant. Dkk1 plays a major role in the development of bone lesions caused by multiple myeloma. In parallel with the initial findings activation of Dkk1 expression by HBZ was abrogated by siRNA-mediated knockdown of p300 CBP or by a truncated form of p300 containing the KIX domain. Among HTLV-1-infected T-cell lines tested the detection of Dkk1 mRNA partially correlated with a threshold level of HBZ mRNA. In addition an uninfected and an HTLV-1-infected T-cell line transfected