Elongation factor 2 in cancer: a promising therapeutic target in protein translation

Song P, Yang F, Jin H, Wang X. The regulation of protein translation and its implications for cancer. Signal Transduct Target Ther. 2021;6(1):68.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dever TE, Green R. The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb Perspect Biol. 2012;4(7): a013706.

Article  PubMed  PubMed Central  Google Scholar 

Murray J, Savva CG, Shin BS, Dever TE, Ramakrishnan V, Fernandez IS. Structural characterization of ribosome recruitment and translocation by type IV IRES. Elife. 2016. https://doi.org/10.7554/eLife.13567.

Article  PubMed  PubMed Central  Google Scholar 

Rodnina MV. Decoding and recoding of mRNA sequences by the ribosome. Annu Rev Biophys. 2023;52:161–82.

Article  CAS  PubMed  Google Scholar 

Djumagulov M, Demeshkina N, Jenner L, Rozov A, Yusupov M, Yusupova G. Accuracy mechanism of eukaryotic ribosome translocation. Nature. 2021;600(7889):543–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaul G, Pattan G, Rafeequi T. Eukaryotic elongation factor-2 (eEF2): its regulation and peptide chain elongation. Cell Biochem Funct. 2011;29(3):227–34.

Article  CAS  PubMed  Google Scholar 

Garreau de Loubresse N, Prokhorova I, Holtkamp W, Rodnina MV, Yusupova G, Yusupov M. Structural basis for the inhibition of the eukaryotic ribosome. Nature. 2014;513(7519):517–22.

Article  CAS  PubMed  Google Scholar 

Shen Y, Zhang ZC, Cheng S, Liu A, Zuo J, Xia S, et al. PQBP1 promotes translational elongation and regulates hippocampal mGluR-LTD by suppressing eEF2 phosphorylation. Mol Cell. 2021;81(7):1425-38 e10.

Article  CAS  PubMed  Google Scholar 

Chen CY, Fang HY, Chiou SH, Yi SE, Huang CY, Chiang SF, et al. Sumoylation of eukaryotic elongation factor 2 is vital for protein stability and anti-apoptotic activity in lung adenocarcinoma cells. Cancer Sci. 2011;102(8):1582–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Oji Y, Tatsumi N, Fukuda M, Nakatsuka S, Aoyagi S, Hirata E, et al. The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers. Int J Oncol. 2014;44(5):1461–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

NCT01061645. Study of MOC31-PE in antigen positive carcinomas. 2012. https://clinicaltrials.gov/study/NCT01061645. Accessed 1 Feb 2012.

Jana S, Brahma S, Arora S, Wladyka CL, Hoang P, Blinka S, et al. Transcriptional-translational conflict is a barrier to cellular transformation and cancer progression. Cancer Cell. 2023;41(5):853-70 e13.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Knight JR, Vlahov N, Gay DM, Ridgway RA, Faller WJ, Proud C, et al. Rpl24(Bst) mutation suppresses colorectal cancer by promoting eEF2 phosphorylation via eEF2K. Elife. 2021. https://doi.org/10.7554/eLife.69729.

Article  PubMed  PubMed Central  Google Scholar 

Xu B, Jia Q, Liao X, Fan T, Mou L, Song Y, et al. Inositol hexaphosphate enhances chemotherapy by reversing senescence induced by persistently activated PERK and diphthamide modification of eEF2. Cancer Lett. 2024;582: 216591.

Article  CAS  PubMed  Google Scholar 

Malik N, Hay J, Almuhanna HNB, Dunn KM, Lees J, Cassels J, et al. mTORC1-selective activation of translation elongation promotes disease progression in chronic lymphocytic leukemia. Leukemia. 2023;37(12):2414–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu H, Xu L, Yue S, Su H, Chen X, Liu Q, et al. Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation. Cancer Commun (Lond). 2024;44(9):1018–41.

Article  CAS  PubMed  Google Scholar 

Pan M, Zorbas C, Sugaya M, Ishiguro K, Kato M, Nishida M, et al. Glutamine deficiency in solid tumor cells confers resistance to ribosomal RNA synthesis inhibitors. Nat Commun. 2022;13(1):3706.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cheng D, He Z, Zheng L, Xie D, Dong S, Zhang P. PRMT7 contributes to the metastasis phenotype in human non-small-cell lung cancer cells possibly through the interaction with HSPA5 and EEF2. Onco Targets Ther. 2018;11:4869–76.

Article  PubMed  PubMed Central  Google Scholar 

Atkinson GC. The evolutionary and functional diversity of classical and lesser-known cytoplasmic and organellar translational GTPases across the tree of life. BMC Genomics. 2015;16:78.

Article  PubMed  PubMed Central  Google Scholar 

Monkemeyer L, Klaips CL, Balchin D, Korner R, Hartl FU, Bracher A. Chaperone function of Hgh1 in the biogenesis of eukaryotic elongation factor 2. Mol Cell. 2019;74(1):88-100 e9.

Article  PubMed  Google Scholar 

Taylor DJ, Nilsson J, Merrill AR, Andersen GR, Nissen P, Frank J. Structures of modified eEF2 80S ribosome complexes reveal the role of GTP hydrolysis in translocation. EMBO J. 2007;26(9):2421–31.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sengupta J, Nilsson J, Gursky R, Kjeldgaard M, Nissen P, Frank J. Visualization of the eEF2-80S ribosome transition-state complex by cryo-electron microscopy. J Mol Biol. 2008;382(1):179–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Taylor DJ, Devkota B, Huang AD, Topf M, Narayanan E, Sali A, et al. Comprehensive molecular structure of the eukaryotic ribosome. Structure. 2009;17(12):1591–604.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gao YG, Selmer M, Dunham CM, Weixlbaumer A, Kelley AC, Ramakrishnan V. The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science. 2009;326(5953):694–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harms JM, Wilson DN, Schluenzen F, Connell SR, Stachelhaus T, Zaborowska Z, et al. Translational regulation via L11: molecular switches on the ribosome turned on and off by thiostrepton and micrococcin. Mol Cell. 2008;30(1):26–38.

Article  CAS  PubMed  Google Scholar 

Petrychenko V, Peng BZ, A C de A P Schwarzer, Peske F, Rodnina MV, Fischer N. Structural mechanism of GTPase-powered ribosome-tRNA movement. Nat Commun. 2021. 12(1): 5933.

Ogle JM, Brodersen DE, Clemons WM Jr, Tarry MJ, Carter AP, Ramakrishnan V. Recognition of cognate transfer RNA by the 30S ribosomal subunit. Science. 2001;292(5518):897–902.

Article  CAS  PubMed  Google Scholar 

Flis J, Holm M, Rundlet EJ, Loerke J, Hilal T, Dabrowski M, et al. tRNA Translocation by the Eukaryotic 80S Ribosome and the Impact of GTP Hydrolysis. Cell Rep. 2018;25(10):2676-88 e7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Demeshkina N, Jenner L, Westhof E, Yusupov M, Yusupova G. A new understanding of the decoding principle on the ribosome. Nature. 2012;484(7393):256–9.

Article  CAS  PubMed  Google Scholar 

Chen C, Stevens B, Kaur J, Cabral D, Liu H, Wang Y, et al. Single-molecule fluorescence measurements of ribosomal translocation dynamics. Mol Cell. 2011;42(3):367–77.

Article  CAS  PubMed  PubMed Central 

留言 (0)

沒有登入
gif