2005 Fiscal Year Final Research Report Summary
Investigation of the regulation mechanism of metastasis by RhoGDI in colon cancer.
| Project/Area Number |
16590642
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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 |
Gastroenterology
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
OTA Takahide Kanazawa Med.Univ., Med.Res.Inst., Associate Prof., 総合医学研究所, 助教授 (10152141)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Masayo Kanazawa Med.Univ., School of Medicine, Research Assistant, 医学部, 助手 (30199632)
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| Project Period (FY) |
2004 – 2005
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| Keywords | RhoGDI / LyGDI / D4GDI / RhoGDI2 / RhoGDIβ / metastasis / colon cancer / FAK / anoikis / apoptosis / src |
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| Research Abstract |
We had shown that Δ166-201-D4GDI (LyGDI/RhoGDIβ/RhoGDI2) lacking the C-terminal 36 amino acid residues promoted the metastasis by constitutively activating Racl signaling pathway at the cell membrane. Here, we showed that neither Δ166-201-D4GDI nor Δ169-204-RhoGDIα, which was C-terminal deleted form of RhoGDIα corresponding to Δ166-201-D4GDI, had a transforming activity in vitro. When the truncated form lacking only C-terminal 6 amino acid (Δ196-201-D4GDI) was expressed in the cells, it also interacted with Racl-GTP and increased the amount of Racl-GTP in the cell. It has been known that the deletion of four to eight amino acid residues at C-terminal severely impaired the function of RhoGDI and that this region is important for the formation of isoprenoid binding pocket to interact with the isoprenoid covalently attached to C-terminal cysteine of Rho family proteins. Recently, it was reported that RhoGDI with the impaired isoprenoid binding pocket functioned dominant negatively, that is, it activated Rho family proteins. These facts indicate that the promotion of metastasis byΔ166-201-D4GDI is due to the inability of this mutant to regulate Rho family proteins through the interaction with isoprenyl moiety of these proteins.
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Research Products
(8 results)
