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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: ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells. | RETROVIROLOGY Non-ATI_ATL ATF3 an HTLV-1 bZip factor binding protein promotes proliferation of adult T-cell leukemia cells Hagiya et al. Hagiya et al. Retrovirology 2011 8 19 http www.retrovirology.com content 8 1 19 17 March 2011 BioMed Central Hagiya et al. Retrovirology 2011 8 19 http www.retrovirology.eom content 8 1 19 RESEARCH RETR0VIR0L0GY Open Access ATF3 an HTLV-1 bZip factor binding protein promotes proliferation of adult T-cell leukemia cells 1 Ix P I-.I 2 1 Keita Hagiya Jun-ichirou Yasunaga Yorifumi Satou Koichi Ohshima Masao Matsuoka Abstract Background Adult T-cell leukemia ATL is an aggressive malignancy of CD4 T-cells caused by human T-cell leukemia virus type 1 HTLV-1 . The HTLV-1 bZIP factor HBZ gene which is encoded by the minus strand of the viral genome is expressed as an antisense transcript in all ATL cases. By using yeast two-hybrid screening we identified activating transcription factor 3 ATF3 as an HBZ-interacting protein. ATF3 has been reported to be expressed in ATL cells but its biological significance is not known. Results Immunoprecipitation analysis confirmed that ATF3 interacts with HBZ. Expression of ATF3 was upregulated in ATL cell lines and fresh ATL cases. Reporter assay revealed that ATF3 could interfere with the HTLV-1 Tax s transactivation of the 5 proviral long terminal repeat LTR doing so by affecting the ATF CRE site as well as HBZ. Suppressing ATF3 expression inhibited proliferation and strongly reduced the viability of ATL cells. As mechanisms of growth-promoting activity of ATF3 comparative expression profiling of ATF3 knockdown cells identified candidate genes that are critical for the cell cycle and cell death including cell division cycle 2 CDC2 and cyclin E2. ATF3 also enhanced p53 transcriptional activity but this activity was suppressed by HBZ. Conclusions Thus ATF3 expression has positive and negative effects on the proliferation and survival of ATL cells. HBZ impedes its negative .
