Regulation of cellular growth and differentiation by novel kinase like proteins, TRB family
| Project/Area Number |
18590067
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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 |
Biological pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
HAYASHI Hidetoshi Nagoya City University, Graduate School of Pharmaceutical Sciences, Associate Professor (80198853)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | TRB3 / cell cycle / CDC25A / protein degradation / adipocyte / PPARγ / PPARγ / TRB1 / DNA傷害 |
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| Research Abstract |
We recently found that a novel pseudokinase TRB3 was induced by endoplasmic reticulum (ER) stress and regulated the ER stress-inducible apoptosis. It was recently reported that TRB3 was highly expressed in some kind of cancers. Then we examined the function of TRB3 in the cell proliferation from the viewpoint of the cell cycle. The expression level of ectopic CDC25A, one of the cell cycle associated phosphatases, was down-regulated by TRB3 in HeLa cells. On the other hand, endogenous CDC25A level was increased when TRB3 was knockdowned by using the RNAi method. We have observed that TRB3 expressed in a cell cycle dependent manner and this expression pattern was reversely correlated with that of CDC25A at the G2/M phase. When we examined the effect of TRB3 knockdown on the cell cycle, its progression was delayed at the G2/M phase and the down-regulation of CDC25A at the M/G1 phase was significantly suppressed. These results suggest that TRB3 is a modulator of cell cycle progression at t
… More
he G2/M phase and that the inhibition of CDC25A expression will be one of the targets of TRB3.
Next, the influence on the cell differentiation was examined. When we had examined the expression level of the endogenous TRB3 in the adipocyte differentiation process using a mouse preadipocyte cell line, 3T3-L1 cell, its expression have temporarily decreased at the early stage, and then have gradually increased according to the cell differentiation at mRNA and protein level. This expression profile was closely related to the appearance of the stress-inducible transcription factor CHOP10/gadd153. When TRB3 was over-expressed in 3T3-L1 cells, the gross amount of intracellular triglyceride and the mRNA expression level of the downstream targets of PPARγ, which is one of the mastering regulator of adipocyte differentiation. On the other hand, when TRB3 mRNA level was impaired by shRNA method, the adipocyte differentiation was potently obstructed. Moreover, TRB3 and PPARγ were associated each other in the cells, and the adipocyte differentiation induced by PPARγ overexpression was strongly suppressed by the ectopic expression of TRB3. It was shown that TRB3 regulates the adipocyte differentiation by negatively controlling the transcriptional activity of PPARγ. Less
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Report
(3 results)
Research Products
(95 results)
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[Journal Article] CCAAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation.2006
Author(s)
K.Shirakawa, S.Maeda, T.Gotoh, M.Hayashi, K.Shinomiya, S.Ehata, R.Nishimura, M.Mori, K.Onozaki, H.Hayashi, E.Ogata, K.Miyazono, T.Imamura
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Journal Title
Molecular and Cellular Biology 26(16)
Pages: 6105-6116
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