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Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes.
Int J Mol Sci. 2020 Jun 27; 21(13)IJ

Abstract

The eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for the viability of the cells whose proposed function is to prevent the stalling of the ribosomes during translation elongation. eIF5A activity requires a unique and functionally essential post-translational modification, the change of a lysine to hypusine. eIF5A is recognized as a promoter of cell proliferation, but it has also been suggested to induce apoptosis. To date, the precise molecular mechanism through which eIF5A affects these processes remains elusive. In the present study, we explored whether eIF5A is involved in controlling the stress-induced expression of the key cellular regulator p53. Our results show that treatment of HCT-116 colon cancer cells with the deoxyhypusine (DHS) inhibitor N1-guanyl-1,7-diamineheptane (GC7) caused both inhibition of eIF5A hypusination and a significant reduction of p53 expression in UV-treated cells, and that eIF5A controls p53 expression at the level of protein synthesis. Furthermore, we show that treatment with GC7 followed by UV-induced stress counteracts the pro-apoptotic process triggered by p53 up-regulation. More in general, the importance of eIF5A in the cellular stress response is illustrated by the finding that exposure to UV light promotes the binding of eIF5A to the ribosomes, whereas UV treatment complemented by the presence of GC7 inhibits such binding, allowing a decrease of de novo synthesis of p53 protein.

Authors+Show Affiliations

Division of Cancer Therapeutics, The Institute of Cancer Research, London SW7 3RP, UK.Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291/324, 00161 Rome, Italy.Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291/324, 00161 Rome, Italy.Department of Life and Environmental Science, Polytechnic University of Marche, 60131 Ancona, Italy.Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291/324, 00161 Rome, Italy.Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 291/324, 00161 Rome, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32605139

Citation

Martella, Marianna, et al. "Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress P53 Translation and Alters the Association of eIF5A to the Ribosomes." International Journal of Molecular Sciences, vol. 21, no. 13, 2020.
Martella M, Catalanotto C, Talora C, et al. Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes. Int J Mol Sci. 2020;21(13).
Martella, M., Catalanotto, C., Talora, C., La Teana, A., Londei, P., & Benelli, D. (2020). Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes. International Journal of Molecular Sciences, 21(13). https://doi.org/10.3390/ijms21134583
Martella M, et al. Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress P53 Translation and Alters the Association of eIF5A to the Ribosomes. Int J Mol Sci. 2020 Jun 27;21(13) PubMed PMID: 32605139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of Eukaryotic Translation Initiation Factor 5A (eIF5A) Hypusination Suppress p53 Translation and Alters the Association of eIF5A to the Ribosomes. AU - Martella,Marianna, AU - Catalanotto,Caterina, AU - Talora,Claudio, AU - La Teana,Anna, AU - Londei,Paola, AU - Benelli,Dario, Y1 - 2020/06/27/ PY - 2020/05/25/received PY - 2020/06/17/revised PY - 2020/06/25/accepted PY - 2020/7/2/entrez PY - 2020/7/2/pubmed PY - 2020/7/2/medline KW - GC7 KW - colon cancer cell lines KW - eIF5A KW - p53 JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 13 N2 - The eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for the viability of the cells whose proposed function is to prevent the stalling of the ribosomes during translation elongation. eIF5A activity requires a unique and functionally essential post-translational modification, the change of a lysine to hypusine. eIF5A is recognized as a promoter of cell proliferation, but it has also been suggested to induce apoptosis. To date, the precise molecular mechanism through which eIF5A affects these processes remains elusive. In the present study, we explored whether eIF5A is involved in controlling the stress-induced expression of the key cellular regulator p53. Our results show that treatment of HCT-116 colon cancer cells with the deoxyhypusine (DHS) inhibitor N1-guanyl-1,7-diamineheptane (GC7) caused both inhibition of eIF5A hypusination and a significant reduction of p53 expression in UV-treated cells, and that eIF5A controls p53 expression at the level of protein synthesis. Furthermore, we show that treatment with GC7 followed by UV-induced stress counteracts the pro-apoptotic process triggered by p53 up-regulation. More in general, the importance of eIF5A in the cellular stress response is illustrated by the finding that exposure to UV light promotes the binding of eIF5A to the ribosomes, whereas UV treatment complemented by the presence of GC7 inhibits such binding, allowing a decrease of de novo synthesis of p53 protein. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32605139/Inhibition_of_Eukaryotic_Translation_Initiation_Factor_5A_(eIF5A)_Hypusination_Suppress_p53_Translation_and_Alters_the_Association_of_eIF5A_to_the_Ribosomes L2 - https://www.mdpi.com/resolver?pii=ijms21134583 DB - PRIME DP - Unbound Medicine ER -
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