p55Cdc/cdc20 overexpression promotes early g1/s transition in myeloid cells.

Abstract

p55Cdc/Cdc20 is expressed in cycling mammalian cells and has been shown to be an activator of the mitotic spindle assembly checkpoint. We previously showed that overexpression of p55Cdc/Cdc20 in myeloid cells resulted in accelerated apoptosis and inhibition of granulocyte differentiation in the murine myeloid cell line 32Dcl3. p55Cdc/Cdc20 protein expression is detected in cells at late G1 phase of the cell cycle but is maximal during G2 phase. We report in this paper that inducible expression of p55Cdc/Cdc20 in 32Dcl3 cells results in premature transition from G1 to S phase. To characterize the mechanism of this early transition, we examined the expression of critical regulatory proteins during the cell cycle. Although expression of cyclin D, cyclin E, cdk2, and cdc2 did not change significantly between p55Cdc/Cdc20-overexpressing and control cells, p27Kip1 protein levels were lower and cdk2 activity higher during G1 to S transition in p55Cdc/Cdc20-overexpressing cells compared to control cells. Cyclin B1 levels were lower at early G1 phase in cells overexpressing p55Cdc/Cdc20. Our results suggest that p55Cdc/Cdc20 may play an important role in G1 to S transition during myelopoiesis.