Geldanamycin induces G2 arrest in U87MG glioblastoma cells through downregulation of Cdc2 and cyclin B1

Cell cycle progression requires precise expression and activation of several cyclins and cyclin-dependent kinases. Geldanamycin (GA) affects cell cycle progression in various kinds of cells. We analyzed GA-induced cell cycle regulation in glioblastoma cells. GA-induced G2 or M arrest in glioblastoma cells in a cell line-dependent manner. GA decreased the expression of Cdc2 and cyclin B1 in U87MG cells. And phosphorylated Cdc2 decreased along with Cdc2 in the GA-treated cells. This cell line showed G2 arrest after GA treatment. in contrast, GA failed to down-regulate these cell cycle regulators in U251MG cells. In U251MG cells, the cell cycle was arrested at M phase in addition to G2 by GA. Next, we analyzed the mechanism of the GA-induced regulation of Cdc2 and cyclin B1 in U87MG cells. Cdc2 and cyclin B1 were ubiquitinated by GA. MG132 abrogated the GA-induced decrease of Cdc2 and cyclin B1 indicating that these proteins were degraded by proteasomes. In conclusion, GA controls the stability of Cdc2 and cyclin B1 in glioblastomas cell species-dependently. Cdc2 and cyclin B1 might be responsible for the different responses of glioblastoma cell lines to GA. (c) 2007 Elsevier Inc. All rights reserved.