2001 Fiscal Year Final Research Report Summary
The regulation mechanism of degradation of p35 CDK5 activation subunit in neurons
| Project/Area Number |
12680700
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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 |
Cell biology
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| Research Institution | Tokyo Metropolitan University |
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Principal Investigator |
HISANAGA Shin-ichi Graduate School of Science, Professor, 理学研究科, 教授 (20181092)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Taro Graduate School of Science, Research Assistant, 理学研究科, 助手 (70301413)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Neuron / Cdk5 / proteasome / Calpain / phosphorylation / Neuronal cell death |
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| Research Abstract |
Cdk5, a cdc2-related kinase expressed in postmitotic neurons, is activated by association with a brain-specific activator, p35. It has been suggested that the conversion of p35 to p25 by the protease calpain is involved in neuronal cell death. On the other hand, p35 protein is rapidly turned over via proteasomal degradation in living neurons. Here, we show that the phosphorylation of p35 is involved in the control of its proteolytic degradation, and that the phosphorylation status of p35 changes in a developmental manner. The phosphorylated form of p35 is resistant to cleavage by calpain and is more susceptible to proteasomal degradation. The unphosphorylated form of p35 is more resistant to proteasomal degradation but is more susceptible to calpain-dependent cleavage to produce p25. Autophosphorylation of p35 by Cdk5 suppresses the cleavage to p25 by calpain, whereas autophosphorylation facilitates the proteasomal degradation of p35. A phosphorylated form of p35 is more prevalent in the fetal brain, whereas the unphosphorylated form of p35 occurs in the adult brain. These results suggest that the autophosphorylation of p35 serves as a protective mechanism that suppresses the generation of p25 in developing brains.
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Research Products
(14 results)
