OVER-EXPRESSION OF P55CDC INHIBITS GRANULOCYTE DIFFERENTIATION AND ACCELERATES APOPTOSIS IN MYELOID CELLS

p55Cdc is a protein identified in cycling mammalian cells. It is highl y expressed in proliferating but not in differentiated or growth-arres ted cells. Structurally, p55Cdc is similar to the Cdc4 and Cdc20 prote ins, which have been proposed to regulate DNA synthesis and mitosis in Saccharomyces cerevisiae. To define the role of p55Cdc during myelopo iesis, me studied the expression and regulation of this protein in res ponse to the hematopoietic growth factors, granulocyte-macrophage colo ny stimulating factor (GM-CSF) and granulocyte-colony stimulating fact or (G-CSF). We analysed the time course of expression of p55Cdc in res ponse to GM-CSF and G-CSF stimulation in the murine factor-dependent m yeloid leukemic cell line, 32Dc13, and demonstrated differential regul ation of p55Cdc in response to these two growth factors, Over-expressi on of p55Cdc resulted in acceleration of apoptosis in growth factor- a nd serum-free conditions, although no difference was observed in the r ate of cell proliferation, Decreases in p55Cdc protein levels correlat ed with cells undergoing apoptosis, p55Cdc over-expression also inhibi ted granulocyte differentiation of 32Dc13 cells treated with G-CSF, Ou r studies suggest that p55Cdc regulation is critical for normal cell c ycle control during myeloid cell proliferation and differentiation.