The p53 tumor suppressor gene plays a role in controlling a G(1) phase checkpoint. The WAF1/CIP1 gene with encodes p21(WAF1/CIP1) protein, an inhibitor of cyclin-dependent kinases, is a downstream mediator of p53 function, We examined expression of the WAF1/CIP1 gene and its relationship to growth arrest and differentiation in p53-null human leukemic cell Lines. We show that p53-independent induction of WAF1/CIP1 occurs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitamin D-3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growth arrest associated with monocyte-macrophage differentiation. The present studies support the idea that WAF1/CIP1 gene expression can be regulated through multiple mechanisms, suggesting that strategies may be designed to restore the G(1) checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.

P53-INDEPENDENT INDUCTION OF WAF1/C1P1 IN HUMAN LEUKEMIA-CELLS IS CORRELATED WITH GROWTH ARREST ACCOMPANYING MONOCYTE/MACROPHAGE DIFFERENTIATION

TRAVALI, Salvatore;
1995-01-01

Abstract

The p53 tumor suppressor gene plays a role in controlling a G(1) phase checkpoint. The WAF1/CIP1 gene with encodes p21(WAF1/CIP1) protein, an inhibitor of cyclin-dependent kinases, is a downstream mediator of p53 function, We examined expression of the WAF1/CIP1 gene and its relationship to growth arrest and differentiation in p53-null human leukemic cell Lines. We show that p53-independent induction of WAF1/CIP1 occurs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitamin D-3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growth arrest associated with monocyte-macrophage differentiation. The present studies support the idea that WAF1/CIP1 gene expression can be regulated through multiple mechanisms, suggesting that strategies may be designed to restore the G(1) checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/8474
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