Programmed cell death 4 (PDCD4) suppresses translation initiation by specifically inhibiting the helicase activity of eukaryotic translation initiation factor 4A (eIF4A), a component of the translation initiation complex and by competing with eIF4G, a second component of the translation initiation complex, for binding to eIF4A. In response to mitogens, PDCD4 was rapidly phosphorylated on Ser67 by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase SCF-β (TRCP). It has been shown th at the protein is specifically phosphorylated on Ser67 and Ser457 by Akt, both in vitro and in vivo. This phosphorylation causes nuclear translocation of PDCD4.
