The reference OMIM entry for this protein is 602223

Eukaryotic translation initiation factor 4e-binding protein 1; eif4ebp1
4ebp1

CLONING

Pause et al. (1994) used interaction cloning to identify 2 novel proteins that interacted with eIF4E (133440), and termed these binding proteins 4EBP1 and 4EBP2 (602224). Pause et al. (1994) reported that the 4EBP1 gene encodes a 118-amino acid polypeptide that is 56% identical to that of 4EBP2. Rat PHAS-I was isolated as a protein phosphorylated in response to insulin in rat adipose tissue. PHAS-I is phosphorylated in response to growth factors and phorbol esters. Pause et al. (1994) noted that the 4EBP1 amino acid sequence was 93% identical to the rat protein PHAS-I, thus representing the human homolog.

GENE FUNCTION

Pause et al. (1994) showed that insulin treatment of adipose cells increased the phosphorylation of 4EBP1 and reduced the interaction of 4EBP1 with eIF4E. The authors speculated that the dissociation of the eIF4E binding proteins may be responsible for the enhanced translational activity in adipose tissue upon insulin treatment. Rousseau et al. (1996) showed that 4EBP1 and 4EBP2 are negative regulators of cell growth. They found that overexpression of either 4EBP1 or 4EBP2 could partially reverse the phenotype of cells transformed by v-src (see 190090) or Ha-v-ras (see 190020). By Northern blot analysis, Tsukiyama-Kohara et al. (1996) showed that 4EBP1 is expressed in most tissues, with highest levels seen in adipose tissue, pancreas, and skeletal muscle. The authors noted that 4EBP1 is more strongly phosphorylated in response to insulin treatment than is 4EBP2, suggesting that 4EBP1 may be more significantly involved in insulin-mediated control pathways. In mammals, MTOR (601231) cooperates with PI3K (see 171834)-dependent effectors in a biochemical signaling pathway to regulate the size of proliferating cells. Fingar et al. (2002) presented evidence that rat S6k1 alpha-II (608938), Eif4e, and Eif4ebp1 mediate Mtor-dependent cell size control. Colina et al. (2008) showed that translational control is critical for induction of type I interferon (see 147570) production. In mouse embryonic fibroblasts lacking the translational repressors 4Ebp1 and 4Ebp2, the threshold for eliciting type I interferon production is lowered. Consequently, replication of encephalomyocarditis virus, vesicular stomatitis virus, influenza virus, and Sindbis virus is markedly suppressed. Furthermore, Colina et al. (2008) showed that mice with both 4Ebp1 and 4Ebp2 genes knocked out are resistant to vesicular stomatitis virus infection, and this correlates with an enhanced type I interferon production in plasmacytoid dendritic cells and the expression of interferon-regulated genes in the lungs. The enhanced type I interferon response of 4Ebp1 -/- 4Ebp2 -/- double knockout mouse embryonic fibroblasts is caused by upregulation of interferon regulatory factor-7 (Irf7; 605047) mRNA translation. Colina et al. (2008) found that their findings highlighted the role of 4EBPs as negative regulators of type I interferon production, via translational repression of IRF7 mRNA. Dowling et al. (2010) inhibited the mTORC1 (601231) pathway in cells lacking EIF4EBP1, EIF4EBP2 (602224), and EIF4EBP3 (603483) and analyzed the effects on cell size, cell proliferation, and cell cycle progression. Although the EIF4EBPs had no effect on cell size, they inhibited cell proliferation by selectively inhibiting the translation of mRNAs that encode proliferation-promoting proteins and proteins involved in cell cycle progression. Thus, Dowling et al. ( ... More on the omim web site

Subscribe to this protein entry history

Dec. 10, 2018: Protein entry updated
Automatic update: model status changed

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 602223 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).