Cyclin-dependent kinase 5 regulates E2F transcription factor through phosphorylation of Rb protein in neurons
Cyclin-dependent kinase 5 regulates E2F transcription factor through phosphorylation of Rb protein in neurons
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DOI：
10.4161/cc.20009
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发表时间：
2012-04-15
期刊：
影响因子：
4.3
通讯作者：
Kulkarni, Ashok B.
中科院分区：
文献类型：
--
作者：
Futatsugi, Akira;Utreras, Elias;Kulkarni, Ashok B.
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Recent studies have shown the involvement of cyclin-dependent kinase 5 (Cdk5) in cell cycle regulation in postmitotic neurons. In this study, we demonstrate that Cdk5 and its co-activator p35 were detected in the nuclear fraction in neurons and Cdk5/p35 phosphorylated retinoblastoma (Rb) protein, a key protein controlling cell cycle re-entry. Cdk5/p35 phosphorylates Rb at the sites similar to those phosphorylated by Cdk4 and Cdk2. Furthermore, increased Cdk5 activity elevates activity of E2F transcription factor, which can trigger cell cycle re-entry, leading to neuronal cell death. A normal Cdk5 activity in neurons did not induce E2F activation, suggesting that Cdk5 does not induce cell cycle re-entry under normal conditions. Taken together, these results indicate that Cdk5 can regulate cell cycle by its ability to phosphorylate Rb. Most importantly, increased Cdk5 activity induces cell cycle re-entry, which is especially detrimental for survival of postmitotic neurons.