IUBMB Life · 1999 · 19 citations · 0 references
Life SciencesCell BiologyMolecular BiologyApoptosisCell ProliferationMolecular Cell BiologyCell Cycle ControlCell Cycle TransitionsCell-cycle ArrestCell-cycle CheckpointsCell-cycle RegulationCyclin-dependent KinasesCdk InhibitorsCell Cycle Arrest MechanismsCell Cycle DynamicsCell Cycle InhibitionCell Cycle InhibitorsG2/m TransitionHeat Shock Protein InhibitorsM Phase Arrest
Geldanamycin (GA), a benzoquinone ansamycin, is one of the specific inhibitors of 90-kDa heat shock protein and induces growth inhibition and apoptosis in certain cancer cell lines. We have investigated the mechanism of GA-induced growth inhibition in K562 erythroleukemic cells. DNA flow-cytometric analysis indicated that GA-induced growth arrest was associated with G2/M phase arrest of the cell cycle. GA treatment down-regulated the expression of cyclin B1 and inhibited phosphorylation of Cdc2 protein, both key regulatory proteins at the G2/M boundary. GA also markedly inhibited the Cdc2 kinase activity, which may be in part a result of up-regulation of p27KIP1 by GA. The present results suggest a novel mechanism that p27KIP1 could be involved in the regulation of G2 to M phase transition.