Over-expression of p55Cdc inhibits granulocyte differentiation and accelerates apoptosis in myeloid cells.
p55Cdc is a protein identified in cycling mammalian cells. It is highly expressed in proliferating but not in differentiated or growth-arrested cells. Structurally, p55Cdc is similar to the Cdc4 and Cdc20 proteins, which have been proposed to regulate DNA synthesis and mitosis in Saccharomyces cerevisiae. To define the role of p55Cdc during myelopoiesis, we studied the expression and regulation of this protein in response to the hematopoietic growth factors, granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF). We analysed the time course of expression of p55Cdc in response to GM-CSF and G-CSF stimulation in the murine factor-dependent myeloid leukemic cell line, 32Dc13, and demonstrated differential regulation of p55Cdc in response to these two growth factors. Over-expression of p55Cdc resulted in acceleration of apoptosis in growth factor- and serum-free conditions, although no difference was observed in the rate of cell proliferation. Decreases in p55Cdc protein levels correlated with cells undergoing apoptosis. p55Cdc over-expression also inhibited granulocyte differentiation of 32Dc13 cells treated with G-CSF. Our studies suggest that p55Cdc regulation is critical for normal cell cycle control during myeloid cell proliferation and differentiation.
Kao
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Division of Hematology-Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, California 91320-1789, USA.
Lin
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M
O'Shea-Greenfield
A
A
Weinstein
J
J
Sakamoto
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KM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D019556:COS Cells; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D051381:Rats; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects
D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; C577494:Cdc20 protein, rat; D018797:Cell Cycle Proteins; D011506:Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor