FunctionInhibits 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.
Tissue specificityUp-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma.
Sequence similaritiesBelongs to the PDCD4 family. Contains 2 MI domains.
DomainBinds EIF4A1 via both MI domains.
Post-translational modificationsPolyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation.
Cellular localizationNucleus. 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.
Fay MM et al. Enhanced Arginine Methylation of Programmed Cell Death 4 Protein during Nutrient Deprivation Promotes Tumor Cell Viability. J Biol Chem289:17541-17552 (2014).
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White K et al. Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis. Hypertension64:185-94 (2014).
Read more (PubMed: 24732886) »