Akt-induced promotion of cell-cycle progression at G2/M phase involves upregulation of NF-Y binding activity in PC12 cells

Akt is a key downstream effector of the PI3K signaling pathway and plays a role in cell growth and survival. Expression of a myristoylated constitutively active form of Akt (myr-Akt) in PC12 cells could override cell-growth arrest at G(2)/M phase and apoptosis that were induced by etoposide treatment. On the other hand, inactivation of Akt by expression of its dominant negative mutant form (km-Akt) inhibited cell proliferation by arresting the cells at G(2)/M phase. Expression of myr-Akt also led to an increase in the protein and mRNA levels of CDK1 and cyclin B1. Furthermore, EMSA data revealed that expression of myr-Akt promoted the binding of NF-Y to the consensus CCAAT promoter sequence, whereas expression of km-Akt almost completely abolished it. Moreover, the Akt activity was minimal in the cells that were arrested at G(2)/M phase by nocodazole treatment, but reached to a maximal level as the cells progressed to mitosis and G, phase upon removal of the drug. Treatment with Akt inhibitors, but not with those of MEK or p70S6K, blocked the release of the cells from the nocodazole-induced G(2)/M arrest, further revealing that the Akt activity is required for G(2)/M phase transition. These results suggest that Akt facilitate cell-cycle progression at G(2)/M phase in PC12 cells and this Akt activity is correlated with upregulation of NF-Y DNA-binding activity and cyclin B1/CDK1 gene expression. J. Cell. Physiol. 205: 270-277, 2005. (c) 2005 Wiley-Liss, Inc.