| Project/Area Number |
13480241
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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 |
Cell biology
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| Research Institution | Aichi Cancer Center |
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Principal Investigator |
INAGAKI Masaki Div. of Biochemistry, Chief, 発がん制御研究部, 部長 (30183007)
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| Co-Investigator(Kenkyū-buntansha) |
IZAWA Ichiro Div. of Biochemistry, Senior Researcher, 発がん制御研究部, 主任研究員 (20311441)
NAGATA Koh-ichi Div. of Biochemistry, Section Head, 発がん制御研究部, 室長 (50252143)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2002: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2001: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Intermediate filament / Protein phosphorylation / site-and phosphorylation state-specific antibody / Aurora-B kinase / IF bunding protein / 中間径フィラメント / ケラチン / TNF / TRADD / Densin-180 |
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| Research Abstract |
1. We identified Aurora-B as a cleavage furrow (CF) kinase. Aurora-B phosphorylates type III intermediate filaments (Ifs), vimentin, GFAP, and desmin, and the phosphorylation causes reduction of their filament forming ability. We next determined the phosphorylation sites of these Ifs by Aurora-B. IF mutants, in which phosphorylation sites by Aurora-B and/or Rho-kinase are changed to Ala or Gly, cause dramatic defect of filament separation between daughter cells in cytokinesis. These results indicate that Aurora-B coordinately regulates cytokinesis with Rho-kinase through the cleavage furrow-specific phosphorylation of type III Ifs.
2. We identified human TNF receptor 1 (TNFR1)-associated death domain protein (TRADD) to be the keratin 18 (K18)-interacting protein. Endogenous TRADD coimmunoprecipitated with K18, and colocalized with K8/18 filaments in human mammary epithelial cells. Overexpression of the NH_2- terminus (aa 1-270) of K18 containing the TRADD-binding domain as well as overexpression of K8/18 in SW13 cells, which are devoid of keratins, rendered the cells more resistant to killing by TNF. These results suggest that K18 may sequester TRADD to attenuate interactions of TRADD with activated TNFR1 and moderate TNF-induced apoptosis in simple epithelial cells.
3. We isolated δ-catenin/neural plakophilin-related armadillo-repeat protein (NPRAP) as a Densin- 180-interacting protein. Densin-180 is associated in vivo with δ-catenin/NPRAP and may be involved in organization of the synaptic cell-cell junction through interaction with theδ-catenin/NPRAP-N- cadherin complex.
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