Function: 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
By similarity. Ref.10 Ref.13 Ref.15 Ref.22 Ref.23 Ref.24
Subunit structure: Interacts (via MI domains) with EIF4A2
By similarity. Interacts (via MI domains) with EIF4A1 (via N-terminal domain). Heterotrimer with EIF4A1; one molecule of PDCD4 binds two molecules of EIF4A1. Interacts with EIF4G1. May form a complex with EIF4A1 and EIF4G1. The interaction between PDCD4 and EIF4A1 interferes with the interaction between EIF4A1 and EIF4G. When phosphorylated, interacts with BTRC and FBXW11. Ref.15 Ref.22 Ref.23 Ref.24
Subcellular location: Nucleus. Cytoplasm. Note: 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. Ref.7 Ref.10
Tissue specificity: Up-regulated in proliferative cells. Highly expressed in epithelial cells of the mammary gland. Reduced expression in lung cancer and colon carcinoma. Ref.7 Ref.8 Ref.13
Induction: IL2/interleukin-2 stimulation inhibits expression, while IL12/interleukin-12 increases expression. Ref.2
Domain: Binds EIF4A1 via both MI domains. Ref.22 Ref.24
Post-translational modification: Polyubiquitinated, leading to its proteasomal degradation. Rapidly degraded in response to mitogens. Phosphorylation of the phosphodegron promotes interaction with BTRC and proteasomal degradation.Phosphorylated at Ser-67 by RPS6KB1 in response to mitogens; phosphorylation promotes proteasomal degradation of PDCD4. Ref.10 Ref.15
Sequence similarities: Belongs to the PDCD4 family.Contains 2 MI domains.
Sequence caution: The sequence AAB42218.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAH15036.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.
Show more