title: Akt-induced promotion of cell-cycle progression at G2/M phase involves upregulation of NF-Y binding activity in PC12 cells.
abstract: 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 G2/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 G2/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 G2/M phase by nocodazole treatment, but reached to a maximal level as the cells progressed to mitosis and G1 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 G2/M arrest, further revealing that the Akt activity is required for G2/M phase transition. These results suggest that Akt facilitate cell-cycle progression at G2/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.
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Korea.
authors.forename: Sun-Ryung
authors.initials: SR
authors.lastname: Lee
authors.forename: Jae-Han
authors.initials: JH
authors.lastname: Park
authors.forename: Eui Kyun
authors.initials: EK
authors.lastname: Park
authors.forename: Chin Ha
authors.initials: CH
authors.lastname: Chung
authors.forename: Shin-Sung
authors.initials: SS
authors.lastname: Kang
authors.forename: Ok-Sun
authors.initials: OS
authors.lastname: Bang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation; D016195:G2 Phase; D008938:Mitosis; D016716:PC12 Cells; D011233:Precipitin Tests; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation
chemical_list: D023081:CCAAT-Binding Factor; D051057:Proto-Oncogene Proteins c-akt