1998 Fiscal Year Final Research Report Summary
Analysis of sinnalling pathway of apoptosis degradation using PKCδ gene-targeting mice
| Project/Area Number |
09480189
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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 |
Molecular biology
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| Research Institution | Kyushu University |
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Principal Investigator |
NAKAYAMA Kei-ichi Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (80291508)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Shigetsugu Medical Institute of Bioregulation, Kyushu University, Research Assoc., 生体防御医学研究所, 助手 (70294973)
NAKAYAMA Keiko Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 助教授 (60294972)
KITAGAWA Masatoshi Medical Institute of Bioregulation, Kyushu University, Assoc. Prof.., 生体防御医学研究所, 助教授 (50294971)
CHINKAI Yoichi Nippon Roche Research Center Senior Scientist, 生物学部, 主幹研究員
OHNO Shigeo Yokohama City Univ. Med. Sch. Professor, 医学部, 教授 (10142027)
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| Project Period (FY) |
1997 – 1998
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| Keywords | PKCδ / apoptosis / knockout mice / singal transduction / B cell / proliferation control |
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| Research Abstract |
It has been reported that protein kinase Cδ (PKCδ) a subtype of PKC family members, is cleaved by caspase resulting in conversion to activated PKCδ upon apoptosis. The aim of this research project is to elucidate the physiological function of PKCδ by generating mice deficient in PKCδ gene.
We constructed the targeting vector and transfect it into embryonic stem (ES) cells to obtain the homologous recombinant of ES cells for PKCδ locus. According to the standard method to generate gene-ablated mice, PKCδ-deficient mice were produced with the mutant ES cells. The PKCδ-deficient mice were viable, healthy, and not prone to cancer development.
Histlogical examinations of the PKCδ-deficient mice revealed splenomegaly due to abnormal accumulation of T and B lymphocytes. In lymph nodes, increase in the number of B cells was more apparent than that of T cells. In vitro culture experiments showed that PKCδ-deficient B cells grew faster than wild-type B cells.
We concluded that PKCδ is not essential for the apoptosis during development, because of the lack of developmental abnormalities. Furthermore, apoptosis of thymovytes and embryonic fibroblasts from PKCδ-deficient mice seems unaffected. However, the extent of apoptosis in B cells appeared to be reduced, suggesting that PKCδ may play an important role in the signaling pathway of apoptosis in B cells.
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[Publications] Shirane, M., Hatakeyama, S., Hattori, K., Nakayama, K. and Nakayama, K.-I.: "Common pathway for the ubiquitination of 1κBα, 1κBβ, and 1κBε mediated by the F-box protein FWD1"J. Biol. Chem.. 274. 28169-28174 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kitagawa, M., Hatakeyama, S., Shirane, M., Matsumoto, M., Ishida, N., Hattori, K., Nakamichi, I., Kikuchi, A., Nakayama, K.-I., and Nakayama, K.: "An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of β-catenin"EMBO J. 18. 2401-2410 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Hatakeyama, S., Kitagawa, M., Nakayama, K., Shirane, M., Matsumoto, M., Hattori, K., Higashi, H., Nakano, H., Okumura, K., Onoe, K., Good, R. A., and Nakayama, K.-I.: "Ubiquitin-dependent degradation of 1κBβ is mediated by a ubiquitin ligase Skp1/Cul1/F-box protein FWD1"Proc. Natl. Acad. Sci. USA. 96. 3859-3863 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Lorick, K. L., Jensen, J. P., Fang, S. Y., Ong, A. M., Hatakeyama, S., Weissman, A. M.: "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination"Proc. Natl. Acad. Sci. USA. 96. 11364-11369 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Hamasaki, A., Sendo, F., Nakayama, K., Ishida, N., Negishi, I., Nakayama, K.-I. And Hatakeyama, S.: "Accelerated neutrophil apoptosis in mice lacking A1-a, a subtype of the bcl-2-related A1 gene"J. Exp. Med.. 188. 1985-1992 (1999)
Description
「研究成果報告書概要(欧文)」より
