Human cells contain three eIF4E protein isoforms encoded by separate genes. Each is capable of binding to the 5’ mRNA cap and exists in several variants resulting from alternative mRNA splicing. All eIF4E isoforms play important roles in development, cancer and cellular response to stress. Cellular level and activity of the canonical eIF4E1 are tightly regulated by mTOR and Mnk kinases. Overexpression of eIF4E1 can lead to cellular transformation and indeed up to one third of human cancers show an increase in eIF4E1 levels. In addition to its well-recognized role in mRNA silencing and translation in hypoxia, the non-canonical eIF4E2 is one of the proteins whose deregulation creates part of the signature of metastatic cells. In contrast, eIF4E3 has been proposed to act as a tumor suppressor protein. The aim of the proposed project is to use advanced pull-down and chromatography methods followed by LC-MS to purify, analyze and characterize active protein complexes in which the non-canonical members of the eIF4E family occur in human cancer cells, mouse oocytes and early embryos. We offer an enthusiastic team, a well-equipped and well-funded laboratory and close international collaboration with some laboratories at EMBL, Heidelberg.

The candidate should have an expertise in biochemistry and/or molecular biology

Five relevant publications of the research group (lab members are underlined):

Iyyappan, R., Aleshkina, D., Ming, H., Dvoran, M., Kakavand, K., Jansova, D., Del Llano, E., Gahurova, L., Bruce, A. W., Masek, T., Pospisek, M., Horvat, F., Kubelka, M., Jiang, Z. & Susor, A. The translational oscillation in oocyte and early embryo development. Nucleic Acids Res (2023), doi:10.1093/nar/gkad996.

del Llano, E., Masek, T., Gahurova, L., Pospisek, M., Koncicka, M., Jindrova, A., Jansova, D., Iyyappan, R., Roucova, K., Bruce, A. W., Kubelka, M. & Susor, A. Age-related differences in the translational landscape of mammalian oocytes. Aging Cell 19 (2020), doi:10.1111/acel.13231.

Frydrýšková K, Mašek T & Pospíšek M. Changing faces of stress: Impact of heat and arsenite treatment on the composition of stress granules. Wiley Interdiscip Rev RNA. Nov;11(6):e1596. (2020), doi: 10.1002/wrna.1596.

Mrvova, S., Frydryskova, K., Pospisek, M., Vopalensky, V. & Masek, T. Major splice variants and multiple polyadenylation site utilization in mRNAs encoding human translation initiation factors eIF4E1 and eIF4E3 regulate the translational regulators? Molecular Genetics and Genomics 293, 167-186 (2018), doi:10.1007/s00438-017-1375-4.

Frydryskova, K., Masek, T., Borcin, K., Mrvova, S., Venturi, V. & Pospisek, M. Distinct recruitment of human eIF4E isoforms to processing bodies and stress granules. BMC Molecular Biology 17 (2016), doi:10.1186/s12867-016-0072-x.

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