p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation.
The p53 tumor suppressor gene plays a role in controlling a G1 phase checkpoint. The WAF1/CIP1 gene with encodes p21WAF1/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 D3, 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 G1 checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.
Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
W
W
Zhang
L
L
Grasso
C D
CD
McClain
A M
AM
Gambel
Y
Y
Cha
S
S
Travali
A B
AB
Deisseroth
W E
WE
Mercer
D015152:Blotting, Northern; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D018274:Electroporation; D005434:Flow Cytometry; D015870:Gene Expression; D016158:Genes, p53; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D009000:Monocytes / Q000166:cytology; D047428:Protein Kinase Inhibitors; D013755:Tetradecanoylphorbol Acetate; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; D013755:Tetradecanoylphorbol Acetate