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Proteomic analysis of ubiquitin-proteasome effects: insight into the function of eukaryotic initiation factor 5A

Oncogene volume 22, pages 4819–4830 (2003)Cite this article

Abstract

The global effect of ubiquitin–proteasome (UP) inhibitors on leukemic cell proteome was analysed. A total of 39 protein spots, affected by UP inhibitors, were identified, including 11 new apoptosis-associated proteins. They are involved in different cellular functions and four were associated with caspase-3 activation. Eukaryotic initiation factor 5A (eIF-5A) was identified in two spots; however, the peptide mass-fingerprinting for the accumulated one included a peptide with lysine50, indicating that hypusine formation was suppressed during UP inhibitor-induced apoptosis. Hypusine modification ensues immediately following translation of eIF-5A precursor, unless cells are treated with the modification inhibitors diaminoheptane. However, UP inhibitors induced a much stronger accumulation of unmodified eIF-5A compared to the effect of diaminoheptane. We further showed the unmodified eIF-5A was regulated in a proteasome-dependent manner. Inhibition of hypusine formation by diaminoheptane triggered apoptosis, but of particular interest is the finding that eIF-5A expression inhibition by antisense oligodeoxynucleotides significantly enhanced the stimulating effect of GM-CSF on cell growth. Therefore, the eIF-5A accumulation played important roles in the apoptosis induced by UP inhibitors. Moreover, hypusine inhibition in apoptosis was further revealed to be associated with the subcellular localization of eIF-5A. Our data pave the way to a better understanding of the mechanisms by which UP system has been linked to apoptosis.

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Acknowledgements

This work was supported by National High Technology Research and Development Program of China (No. 2001AA233041), and grants from National Natural Science foundation of China (No. 30070377 and 30270299).

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  1. Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing, 100850, China

    Bao-Feng Jin, Kun He, Hong-Xia Wang, Jie Wang, Tao Zhou, Yu Lan, Mei-Ru Hu, Kai-Hua Wei, Song-Cheng Yang, Bei-Fen Shen & Xue-Min Zhang

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Jin, BF., He, K., Wang, HX. et al. Proteomic analysis of ubiquitin-proteasome effects: insight into the function of eukaryotic initiation factor 5A. Oncogene 22, 4819–4830 (2003). https://doi.org/10.1038/sj.onc.1206738

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