The rapid destabilization of p53 mRNA in immortal chicken embryo fibroblast cells

The steady-state levels of p53 mRNA were dramatically lower in immortal chi cken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In t he presence of cycloheximide (CHX), the steady-state levels of p53 mRNA mar kedly increased in immortal CEF cell lines, similar to levels found in prim ary cells. The de novo synthetic rates of p53 mRNA were relatively similar in primary and immortal cells grown in the presence or absence of CHX. Dest abilization of p53 mRNA was observed in the nuclei of immortal, but not pri mary, CEF cells. The half-life of p53 mRNA in primary cells was found to be a relatively long 23 h compared to only 3 It in immortal cells. The expres sion of transfected p53 cDNA was inhibited in immortal cells, but restored upon CHX treatment. The 5'-region of the p53 mRNA was shown to be involved in the rapid p53 mRNA destabilization in immortal cells by expression analy sis of 5'- and 3-deleted p53 cDNAs as well as fusion mRNA constructs of N-t erminal p53 and N-terminal deleted LacZ genes. Together, it is suggestive t hat the downregulation of p53 mRNA in immortal CEF cells occurs through a p ost-transcriptional destabilizing mechanism.