| Project/Area Number |
08458231
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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 | Nara Institute of Science and Technology |
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Principal Investigator |
KATO Jun-ya Nara Institute of Science and Technology Graduate School of Biological Science, Associate Professor, バイオサイエンス研究科, 助教授 (00273839)
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| Project Period (FY) |
1996 – 1998
|
| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | Cyclin / Cdk / Cdk inhibitor / Cell Cycle |
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| Research Abstract |
The cyclin-dependent kinase inhibitor p27^<Kip1> plays an essential role in control of mammalian cell proliferation both in vitro and in vivo. Although p27^<Kip1> mutations are rare in human tumors, reduced expression of the protein correlates well with poor survival among breast and colorectal carcinoma patients, suggesting that disturbance of p27^<Kip1> regulatory mechanisms contributes to neoplasia. Cellular abundance of p27^<Kip1> is controlled translationally or by multiple posttranslational mechanisms including phosphorylation by cyclin E/cdk2 complexes, degradation by the ubiquitin/proteasome pathway, and sequestration by unknown Myc-inducible proteins, cyclin D/cdk4 complexes, or the viral ElA oncoprotein. Here we show that a mouse 38kDa protein encoded by the Jab1 genephysically and specifically interacted with p27^<Kip1>. We demonstrate that overexpression of p38 in mammalian cells specifically translocated p2^<Kip1> from the nucleus to the cytoplasm in a proteasome-dependent manner, and decreased intracellular levels of p27^<Kip1> protein by accelerating its degradation. Furthermore, ectopic p38 expression in mouse fibroblasts partially overcame p27^<Kip1>-mediated Gi arrest, and markedly reduced their serum dependency. Our findings suggest that p38 functions as a negative regulator of p27^<Kip1> by targeting it for degradation.
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