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p55Cdc/Cdc20 Overexpression Promotes Early G₁/S Transition in Myeloid Cells

Department of Pediatrics, UCLA School of Medicine, Los Angeles, California, USA

Key Words. p55Cdc • Cdc20 • Cell cycle • Myeloid cells • G₁ • S

Kathleen M. Sakamoto, M.D., Department of Pediatrics-Hematology/Oncology, A2-311 MDCC, 10833 Le Conte Avenue, Los Angeles, California 90095-1752, USA. Telephone: 310-794-7007; Fax: 310-206-8089; e-mail: kms{at}ucla.edu

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.

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