2001 Fiscal Year Final Research Report Summary
Analysis of a novel GTP-binding protein GSPT involved in translational regulation
| Project/Area Number |
12672106
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HOSHINO Shin-ichi The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Lecturer, 大学院・薬学系研究科, 講師 (40219168)
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| Co-Investigator(Kenkyū-buntansha) |
KONTANI Kenji The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Research fellow, 大学院・薬学系研究科, 助手 (30302615)
NISHINA Hiroshi The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Associate Professor, 大学院・薬学系研究科, 助教授 (60212122)
KATADA Toshiaki The University of Tokyo, Graduate School of Pharmaceutical Sciences, Dept. of Physiol. Chem., Professor, 大学院・薬学系研究科, 教授 (10088859)
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| Project Period (FY) |
2000 – 2001
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| Keywords | mRNA / GTP-binding protein / translation / poly(A) / poly(A)-binding protein / translation termination |
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| Research Abstract |
Translation termination in eukaryote is governed by the two termination factors eRF1 and eRF3/GSPT. GSPT is a GTP-binding protein consisting of unique N-terminal domain and Ef1a-like C-terminal domain. GSPT carries eRF1, which recognizes all three termination codons, to the A site of the ribosome and promotes release of synthesized polypeptide chain from the ribosome. For this reaction the C-domain but not the N-domain of GSPT is demonstrated to be required and sufficient.
In the present study, we investigated functional roles of the N-domain of GSPT. To gain insight into this issue, we first screened a binding partner of the N-domain of GSPT by the yeast two-hybrid system and identified polyadenylate binding protein (PABP1), which is suggested to function in the regulation of mRNA stability and translation initiation. By the use of yeast genetics and biochemical approaches, we demonstrated that GSPT interact with PABP to function as a regulator of both ribosomal shunting and mRNA degradation. These processes are coupled to translation termination. Thus after regulating translation termination, GSPT is found to participate in the next round of translation initiation and degradation of the used mRNA.
In addition to GSPT, structurally homologous genes were identified. eRFS is one of the most homologous genes and has similar two-domain structure, though the function has not been determined. In this study, we also found that the C-domain of eRFS interacts with a novel gene product, eRFL, which we newly identified as a structural homologue of eRF1. In contrast N-domain of eRFS is found to interact functionally with GAPDH, which is known not only as a key glycolytic enzyme but also as an AU-rich element binding protein. These results suggest that in analogous to GSPT, eRFS also functions in the regulation of gene expression at the level of translation and mRNA metabolism.
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[Publications] M. Hara-Yokoyama, Y. Nagatsuka, O. Katsumata, F. Irie, K. Kontani, S. Hoshino, T. Katada, Y. Ono, J. Fujita-Yoshigaki, H. Sugiya, S. Furuyama, Y. Hirabayashi: "Coniplex Gangliosides as Cell Surface Inhibitors for the Ecto-NAD^+ Glycohydrolase of CD38"Biochemistry. 40. 888-895 (2001)
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[Publications] T. Wada, K. Nakagawa, G. Nishitai, J. Seo, H. Kishimoto, T. Watanabe, D. Kitagawa, T. Sasaki, J. M. Penninger, H. Nishina, T. Katada: "Impaired synergistic activation of stress-activated protein kinase SAPK/JNK in ES cells lacking SEK1/MKK4"J. Biol. Chem. 276. 30892-30897 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] D. Kitagawa, S. Tanemura, S. Ohata, N. Shimizu, J. Seo, G. Nishitai, T. Watanabe, K. Nakagawa, H. Kishimoto, T. Wada, T. Tezuka, T. Yamamoto, H. Nishina, T. Katada T: "Activation of extracellular signalregulated kinase by ultraviolet is mediated through Src-dependent epidermal growth factor receptor phosphorylation : Its implication in an anti-apoptotic function"J. Biol. Chem. 277. 366-371 (2002)
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「研究成果報告書概要(欧文)」より
