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Induction of translationally controlled tumor protein (TCTP) by transcriptional and post‐transcriptional mechanisms
Author(s) -
Schmidt Irina,
Fähling Michael,
Nafz Benno,
Skalweit Angela,
Thiele BerndJoachim
Publication year - 2007
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.06069.x
Subject(s) - messenger rna , microbiology and biotechnology , transcriptional regulation , untranslated region , chemistry , forskolin , gene expression , promoter , rna , three prime untranslated region , transcription (linguistics) , gene , downregulation and upregulation , biology , biochemistry , receptor , linguistics , philosophy
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 4β‐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‐crosslinking. 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, nickel, cobalt (1.8–2.3‐fold) and copper (2.5–3.0‐fold), whereas stimulation of TCTP synthesis by copper was mediated by the TCTP mRNA 3′‐UTR (3.2‐fold) but not by the 5′‐UTR (0.5‐fold). mRNA stabilization was found to mediate these effects of cobalt and nickel. Post‐transcriptional regulation was associated with qualitative and quantitative changes in the binding of specific RNA‐binding proteins to UTRs.