p21Cip1/WAF1 is important for differentiation and survival of U937 cells.
Vitamin D3 (VD3) induces monocytic differentiation of U937 cells. Induction of p21Cip1/WAF1 (p21) and subsequent G0/G1 cell-cycle arrest are required in this process. Using a system of inducible expression of ectopic p21, we demonstrated the important role of p21 in the induction of monocytic differentiation in U937 cells. Prior induction of antisense-p21 expression significantly suppressed p21 expression, and resulted in inhibition of VD3-induced U937 differentiation. Moreover, induction of expression of antisense-p21 in VD3-differentiated U937 cells resulted in apoptosis of the cells. This was associated with activation of Cdc2 and caspase-3 like protease. Our results suggest that p21 is required for the initiation of the early steps of differentiation as well as survival of differentiated cells.
Asada
M
M
Department of Virology, The National Children's Medical Research Center, Tokyo, Japan.
Yamada
T
T
Fukumuro
K
K
Mizutani
S
S
D017209:Apoptosis / Q000502:physiology*; D018845:CD11 Antigens / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D014162:Transfection; D020298:U937 Cells; D019287:Zinc Sulfate / Q000494:pharmacology
D018845:CD11 Antigens; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019287:Zinc Sulfate; D020169:Caspases