p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation.
p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation.
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发表时间：
1995-02
期刊：
影响因子：
11.2
通讯作者：
W. Zhang;L. Grasso;C. McClain;A. Gambel;Y. Cha;S. Travali;A. Deisseroth;W. Mercer
中科院分区：
文献类型：
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作者：
W. Zhang;L. Grasso;C. McClain;A. Gambel;Y. Cha;S. Travali;A. Deisseroth;W. Mercer
p53肿瘤抑制基因在控制G1期检查点中起作用。WAF 1/CIP 1基因编码p21 WAF 1/CIP 1蛋白，是细胞周期蛋白依赖性激酶抑制剂，是p53功能的下游介导物。我们研究了WAF 1/CIP 1基因的表达及其与p53缺失的人白血病细胞系生长停滞和分化的关系。我们发现，p53非依赖性诱导WAF 1/CIP 1发生在人白血病细胞处理12-O-十四烷酰佛波醇-13-乙酸酯，冈田酸，或IFN-γ，但不与视黄酸，维生素D3，或DMSO。此外，WAF 1/CIP 1诱导与单核细胞-巨噬细胞分化相关的生长停滞相关。目前的研究支持WAF 1/CIP 1基因表达可以通过多种机制调节的想法，这表明可以设计策略，通过靶向WAF 1/CIP 1诱导的这些p53非依赖性机制来恢复p53缺失细胞中的G1检查点控制。
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.