ATF2 translation is induced under chemotherapeutic drug-mediated cellular stress via an IRES-dependent mechanism in human hepatic cancer Bel7402 cells

Activating transcription factor (ATF) 2 is a member of the ATF/cyclic AMP-responsive element binding protein family, which exhibits both oncogenic and tumor-suppressor functions. In our preliminary experiments, it was observed that the expression of the ATF2 protein was induced following treatment with adriamycin (ADR) and paclitaxel (PTX), which may be regulated by internal ribosome entry segment (IRES)-mediated translation. By constructing a bicistronic vector containing the ATF2 5'-untranslated region (UTR), it was demonstrated that the ATF2 5'-UTR contains an IRES and maps a 30-nucleotide (nt) sequence (from nt 299 to nt ~269), which was essential for the IRES activity. The ATF2 IRES activity exhibited significant variation in different cell lines. In addition, it was observed that ADR and PTX also induced ATF2 IRES activity in Bel7402 cells. The present study has demonstrated that ATF2 translation is initiated via IRES, which is upregulated by ADR and PTX, thus suggesting that the regulation of the IRES-dependent translation of ATF2 may be involved in effecting the cancer cell response to chemotherapeutic drugs-mediated cellular stress.