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Publication : Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex.

First Author  Zhang J Year  2010
Journal  J Neurosci Volume  30
Issue  15 Pages  5219-28
PubMed ID  20392944 Mgi Jnum  J:159853
Mgi Id  MGI:4452555 Doi  10.1523/JNEUROSCI.5628-09.2010
Citation  Zhang J, et al. (2010) Cdk5 suppresses the neuronal cell cycle by disrupting the E2F1-DP1 complex. J Neurosci 30(15):5219-28
abstractText  Neurons that reenter a cell cycle after maturation are at increased risk for death, yet the mechanisms by which a normal neuron suppresses the cycle remain mostly unknown. Our laboratory has shown that cyclin-dependent kinase 5 (Cdk5) is a potent cell cycle suppressor, and we report here on the molecular basis of this activity. Cell cycle suppression by Cdk5 requires its binding to the p35 activator protein. The related p39 and p25 proteins cannot serve as substitutes. Unexpectedly, Cdk5 enzymatic activity is not required to perform this function. Rather, the link to cell cycle regulation is made through the formation of a previously unknown complex consisting of the p35-Cdk5 dimer and E2F1. Formation of this complex excludes the E2F1 cofactor, DP1, thus inhibiting E2F1 binding to the promoters of various cell cycle genes. This anti-cell cycle activity is most likely a neuroprotective function of Cdk5.
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