2006 Fiscal Year Final Research Report Summary
Mechanism of genome instability caused by aberrant expression of SHD1, regulator of centrosome duplication
| Project/Area Number |
17590271
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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 |
Pathological medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
KUWAHARA Kazuhiko Kumamoto University, Graduate School of Medical Sciences, Immunology, Associate Professor, 大学院医学薬学研究部, 助教授 (10263469)
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| Project Period (FY) |
2005 – 2006
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| Keywords | centrosome duplication / genome instability / tumorigenesis / knock-out mice / transgenic mice |
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| Research Abstract |
In order to clarify the role of SHD1 in centrosome duplication, we searched for SHD 1-associated molecules in centrosomes using yeast two-hybrid system and proteomics. One candidate molecule, designated THP1, was identified, but at present we do not show whether THP1 is associated with SHD1 in centrosomes because anti-THP1 Abs we established did not work in Western blot and immunohistochemistry. To demonstrate the functional role of THP1 in vivo, we established B cell-specific THP1-deficient mice. These mice showed sever decreased B cell number, suggesting that B cells did not survive in the absence of THP1. Using NIH3T3 cells, we confirmed the increased apoptosis in THP1 knockdown cells, which was presumably involved in the induction of proapoptotic molecule, Bax.
In Sacaharomyces cerevisiae, Sac3 that is homologous to SHD1 is associated with CDC31, yeast centrin. However, we could not detect the association between SHD1 and centrin, indicating that the mechanism of centrosome duplication in mouse cells is different from that in yeast cells. Moreover, we established SHD1-deficie : it mice, but they did not show apparent abnormalities in comparison to control mice. There is a possibility that other molecule(s) can compensate for the functions of SHD1. Adversely, Balb/c-SHD1 transgenic mice under the control of lck promoter were also prepared to examine whether over-expressed SHD1 is involved in tumorigenesis. They did not bear any tumors in the observation for six months. We need longer observation to get the solid conclusion.
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