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Báo cáo khoa học: Induction of translationally controlled tumor protein (TCTP) by transcriptional and post-transcriptional mechanisms

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Expression of the humanTPT1gene coding for translationally controlled tumor protein (TCTP) was investigated in Calu-6 and Cos-7 cells under the influence of 4b-phorbol 12-myristate 13-acetate (PMA), forskolin, dioxin and the heavy metals copper, nickel and cobalt. | ễFEBS Journal Induction of translationally controlled tumor protein TCTP by transcriptional and post-transcriptional mechanisms Irina Schmidt Michael Fahling Benno Nafz Angela Skalweit and Bernd-Joachim Thiele Charites Universitatsmedizin Berlin Institut fur Vegetative Physiologie Germany Keywords gene expression post-transcriptional control TPT1 gene transcription translationally controlled tumor protein TCTP Correspondence B.-J. Thiele Charites Universitatsmedizin Berlin Institut fur Vegetative Physiologie Tucholskystr. 2 10117 Berlin Germany Fax 49 30 450 528972 Tel 49 30 450 528184 E-mail bernd.thiele@charite.de Received 14 June 2007 revised 23 August 2007 accepted 28 August 2007 doi 10.1111 j.1742-4658.2007.06069.x Expression of the human TPT1 gene coding for translationally controlled tumor protein TCTP was investigated in Calu-6 and Cos-7 cells under the influence of 4p-phorbol 12-myristate 13-acetate PMA forskolin dioxin and the heavy metals copper nickel and cobalt. Transcriptional and post-transcriptional aspects of the mechanism were analyzed by TCTP mRNA protein quantification luciferase reporter gene assays depending on TPT1 promoter sequences or TCTP mRNA 5 3 -UTRs and investigation of the interaction of RNA-binding proteins with UTRs by UV-cross-linking. PMA forskolin dioxin cobalt and nickel induced TCTP expression in 24 h in both cell lines about 2.2-3.2-fold at the mRNA level and 1.6-2.2-fold at the protein level. The highest induction rate 4.5-5.0-fold at the mRNA level and 3.5-4.0-fold at the protein level was observed with copper. TPT1 promoter assays showed transcriptional activation by PMA forskolin and dioxin 2.0-3.1-fold and a 7.0-8.0-fold increase by copper whereas cobalt and nickel had no effect. Deletion analysis revealed that copper-dependent transcriptional control was transmitted by a metal-responsive element residing in the TPT1 promoter. Post-transcriptional activation of TCTP expression was associated with the action of dioxin .