The transformation suppressor gene Pdcd-4 (programmed cell death gene 4) inhibits the tumor-promoter mediated transformation of mouse keratinocytes and is a potential tumor suppressor gene in the development of human lung cancer. Biochemical analysis suggests that the Pdcd-4 protein is involved in protein translation as well as in nuclear events. Pdcd-4 directly interacts with the RNA helicase eIF4A and inhibits protein synthesis by interfering with the assembly of the cap-dependent translation initiation complex. Pdcd-4 also suppresses the transactivation of AP-1 responsive promoters by c-Jun, suggesting that the transformation-suppressor activity of Pdcd-4 might be due, at least in part, to the inhibition of c-Jun activity. In addition to affecting c-Jun phosphorylation, Pdcd-4 blocks the recruitment of the co-activator p300 by c-Jun.
