PDCD4: Proteins and Enzymes

Programmed Cell Death 4 (PDCD4) is a 469 amino acid (aa) protein with a predicted molecular weight of 51.7 kDa that was originally identified in cells undergoing apoptosis. The human protein shares 96% aa sequence identity with the mouse and rat orthologs. The subcellular localization of PDCD4 is primarily nuclear, but it is exported to the cytoplasm via two nuclear export signals upon serum removal. It contains an unstructured N-terminal RNA-binding region and two MA-3 domains. PDCD4 inhibits the initiation of translation via interaction of its MA-3 domains with the RNA helicase eIF4A. PDCD4 itself is inhibited by p70 S6 Kinase-dependent phosphorylation downstream of TOR. The PDCD4 protein is also a well-known tumor suppressor. Gastric cancer patients who express PDCD4 have a higher survival rate compared to patients who do not express PDCD4. Furthermore, its expression is negatively regulated by the oncogenic microRNA, miR-21. PDCD4 has also been reported to have a role in the prevention of epithelial to mesenchymal transition and metastasis in mice.