programmed cell death 4 (neoplastic transformation inhibitor)
Programmed cell death protein 4
Topoisomerase-inhibitor suppressed protein
Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A1 and EIF4G. Inhibits the helicase activity of EIF4A. Modulates the activation of JUN kinase. Down-regulates the expression of MAP4K1, thus inhibiting events important in driving invasion, namely, MAPK85 activation and consequent JUN-dependent transcription. May play a role in apoptosis. Tumor suppressor. Inhibits tumor promoter-induced neoplastic transformation. Binds RNA.
Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma.
Belongs to the PDCD4 family. Contains 2 MI domains.
Binds EIF4A1 via both MI domains.
Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation.
Nucleus. Cytoplasm. Shuttles between the nucleus and cytoplasm. Predominantly nuclear under normal growth conditions, and when phosphorylated at Ser-457. Exported from the nucleus in the absence of serum.