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 coactivator p300 by
c-Jun.