eIF4E (Phospho-Ser²⁰⁹) Rabbit Monoclonal Antibody (Clone RM452)

Eukaryotic translation initiation factor 4E (eIF4E) is a component of the eIF4 complex that specifically binds to the methyl-7-guanosine cap structure at the 5’ end of eukaryotic mRNA to initiate translation.^1,2,3 It is composed of an α/β domain containing one short and three long α-helices and an antiparallel β-sheet.¹ eIF4E is ubiquitously expressed and localized to the nucleus and cytoplasm.⁴ Nuclear eIF4E promotes export of mRNAs that contain the eIF4E sensitivity element (4E-SE) to the cytosol while cytosolic eIF4E, in a complex with eIF4A and eIF4G1/eIF4G3, mediates recruitment of mRNAs to the ribosome to initiate cap-dependent translation.^1,3 eIF14E activity is regulated by eIF4E-binding proteins (4E-BPs), which bind eIF4E to prevent eIF4 complex assembly and subsequent translation.³ Overexpression of eIF4E is observed in approximately 30% of human malignancies, including breast, colon, and head and neck carcinomas and acute myeloid leukemias, particularly myelomonocytic M4 and monocytic M5 subtypes, as well as prostate cancers.^3,5,6 Increased eIF4E expression leads to increased translation of oncogenic mRNAs, such as those encoding VEGF and cyclin D1, and contributes to cancer cell survival and proliferation. Phosphorylation of eIF4E at serine 209 (Ser²⁰⁹) is associated with tumor progression and reduced survival in patients with malignant melanoma, and pharmacologic inhibition of eIF4E phosphorylation is selectively cytotoxic to cancer cells.^7,8 Cayman’s eIF4E (Phospho-Ser²⁰⁹) Rabbit Monoclonal Antibody (Clone RM452) can be used for Western blot (WB) applications.

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1. Marcotrigiano, J., Gingras, A.C., Sonenberg, N., et al. Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell 89(6), 951-961 (1997).

2. Haghighat, A., and Sonenberg, N. eIF4G dramatically enhances the binding of eIF4E to the mRNA 5'-cap structure. The Journal of Biological Chemisty 272(35), 21677-21680 (1997).

3. Piserà, A., Campo, A., and Campo, S. Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment. J. Genet. Genomics 45(1), 13-24 (2018).

4. Topisirovic, I., Culjkovic, B., Cohen, N., et al. The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J. 22(3), 689-703 (2003).

5. Carroll, M., and Borden, K.L. The oncogene eIF4E: Using biochemical insights to target cancer. J. Interferon. Cytokine Res. 33(5), 227-238 (2013).

6. Yin, X., Kim, R.H., Sun, G., et al. Overexpression of eukaryotic initiation factor 4E is correlated with increased risk for systemic dissemination in node-positive breast cancer patients. J. Am. Coll. Surg. 218(4), 663-671 (2014).

7. Carter, J.H., Deddens, J.A., Spaulding, N.R., IV., et al. Phosphorylation of eIF4E serine 209 is associated with tumour progession and resuced survival in malignant melanoma. Brit. J. Cancer 114(4), 444-453 (2016).

8. Gu, Y., Zhou, H., Gan, Y., et al. Small-molecule induction of phospho-eIF4E sumoylation and degradation via targeting its phosphorylated serine 209 residue. Oncotarget 6(17), 15111-15121 (2015).