PT  - JOURNAL ARTICLE
AU  - Jie Zhang
AU  - Huifang Li
AU  - Odessa Yabut
AU  - Haley Fitzpatrick
AU  - Gabriella D'Arcangelo
AU  - Karl Herrup
TI  - Cdk5 Suppresses the Neuronal Cell Cycle by Disrupting the E2F1–DP1 Complex
AID  - 10.1523/JNEUROSCI.5628-09.2010
DP  - 2010 Apr 14
TA  - The Journal of Neuroscience
PG  - 5219--5228
VI  - 30
IP  - 15
4099  - http://www.jneurosci.org/content/30/15/5219.short
4100  - http://www.jneurosci.org/content/30/15/5219.full
SO  - J. Neurosci.2010 Apr 14; 30
AB  - 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.