| Project/Area Number |
63480495
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
YAHARA Ichiro The Tokyo Met. Inst. Med. Sci., Dep. Direct., 細胞生物部門, 部長 (60109957)
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| Co-Investigator(Kenkyū-buntansha) |
IIDA Kazuko The Tokyo Met. Inst. Med. Sci., Res. Assoc., 細胞生物部門, 研究員 (40151229)
MATSUMOTO Seiji The Tokyo Met. Inst. Med. Sci., Res. Assoc., 細胞生物部門, 研究員 (40190532)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | heat shock protein / stress protein / HSP90 / glucocorticoid receptor / steroid hormone receptor / actin / cofilin / nuclear translocation / カゼインキナ-ゼII / コフイリン / カルモデュリン / 熱ショック応答 |
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| Research Abstract |
The following two objects were dealt with in this research. First, molecular features of a major heat shock protein, HSP90 were investigated. Second, upon heat shock, an actin-binding protein, cofilin together with actin are translocated from cytoplasm to nucleus. Molecular characterization of cofilin was performed in order to clarify the mechanism operating in the translocation.
1) We found that HSP90 exist as alpha/alpha and beta/beta homodimers and BETA monomer under the physiological conditions.
2) We showed that 8S-glucocorticoid receptor which is consisted of the GR protein and HSP90 binds actin filaments through its HSP90 moiety. This finding provided new insight into the mechanism of ligand-dependent translocation of GR from the cytoplasm to the nucleus.
3) Casein kinase II forms self-aggregate. We found that HSP90 dissociates CKII aggregates by binding to the kinase and activates its activity.
4) We investigated the molecular properties of an actin-binding protein, cofilin, which had been shown to translocate into the nucleus from the cytoplasm upon heat shock. We have shown that the KKRKK sequence is an nuclear translocation signal. In addition, we have identified domains involved in actin-binding.
5) We have newly cloned cDNAs which encode destrin, another actin-binding protein belonging to the cofilin family. The expression of cofilin and destrin were compared in various mouse tissues.
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