2001 Fiscal Year Final Research Report Summary
The role of crm1 in leptomycin B induced fixation of Xray related potentially lethal damage
| Project/Area Number |
11670897
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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 |
Radiation science
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| Research Institution | Kyushu University |
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Principal Investigator |
KURA Shinobu Faculty of Medical Science, Kyushu University Assistant, 大学院・医学研究院, 助手 (90037391)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Yasuhide Faculty of Medical Science, Kyushu University Assistant, 大学院・医学研究院, 助手 (60263307)
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| Project Period (FY) |
1999 – 2000
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| Keywords | CRM1 / leptomycin B / PLD / スナネズミ / 放射線感受性 |
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| Research Abstract |
Potentially lethal damage (PLD)(1), which is produced preferentially by sparsely ionizing radiations such as X or γ Rays, has shown to be fixed by postirradiation treatments with agents such as caffeine (2) or anisotonic solutions (3). However, the mechanisms of PLD fixation remains to be elusidated. We found that cell killing was enhanced when BHK cells were treated with leptomycinB (LMB) after irradiation. The degree of enhanced cell killing decreased as the interval between irradiation and LMB treatment was prolonged. Enhancement of cell killing was probably due to fixation of PLD by LMB(4). However, cell killing was not enhanced when MGF (Mongolian Gerbil Fetal) cells were treated with LMB after x-irradiation. Nishi K. et al. reported that CRM1 is the cellular target of LMB(5). Recently, Kudo N. et al. found that LMB binds the sulfhydryl group of Cys-529 and that cystein is conserved in those LMB-sensitive organisms such as human and S.pombe, but not in those LMB-insensitive organisms such as S. cerevisiae. Thus, Cys-529 is the most important determinant of LMB-sensitivity of the CRM1 protein. (6)
It seems plausible that MGF CRM1 contain an amino acid change in the 529 position and lost the ability to interact with LMB.
To verify this hypothesis we cloned cDNA encoding CRM1 of MGF cells. The deduced amino acid sequence revealed that the amino acid at the 529 position is cystein which is same as that of LMB-sensitive organisms.
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