2000 Fiscal Year Final Research Report Summary
Cellular cofactors involved in transport of mRNAs of complex retroviruses and hepatitis B virus
| Project/Area Number |
11470079
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SHIDA Hisatoshi Hokkaido Univ.Institute for Genetic Medicine. Professor, 遺伝子病制御研究所, 教授 (00144395)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Masami Hokkaido Univ.Institute for Genetic Medicine. Assistant professor, 遺伝子病制御研究所, 助手 (10322851)
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| Project Period (FY) |
1999 – 2000
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| Keywords | RNA transport / Rev / Rex / CRM1 / multimerization / hepatitis B virus |
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| Research Abstract |
Human CRM1 (hCRM1), a member of exportin family, has dual functions as a receptor for leucine-rich NES and in supporting the multimerization of HTLV-1 Rex and protein. To investigate the mechanism of Rex-CRM1 interaction and multimerization of Rex, we focused on impaired Rex function in rat cells. We cloned a cDNA encoding rat CRM1 (rCRM1) and compared with hCRM1 in Rex function. Our results indicate that rCRM1 does not support Rex function efficiently because of a poor ability to induce Rex multimerization, although it binds strongly to the Rex NES.Detailed comparison of human and rat CRM1 sequences, followed by construction of chimera and mutant CRM1 proteins allowed us to identify the amino acids critical for binding to the Rex NES and for Rex multimerization. These results suggested that the capacity of CRM1 to support Rex multimerization is separable from efficient NES binding, implying a higher order interaction between CRM1 and Rex than simple association via the NES region of Rex.
We also found CRM1 supports multimerization of HIV Rev protein. Carboxy terminal of Rev protein stabilizes the interaction of NES region with CRM1, consequently leading to efficient multimerization of Rev proteins.
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Research Products
(2 results)
