Activation and repression of p21WAF1/CIP1 transcription by RB binding proteins
Activation and repression of p21WAF1/CIP1 transcription by RB binding proteins
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DOI：
10.1038/sj.onc.1202240
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发表时间：
1998-12-31
期刊：
影响因子：
8
通讯作者：
Tyner, AL
中科院分区：
文献类型：
--
作者：
Gartel, AL;Goufman, E;Tyner, AL
Cdk抑制剂p21（WAF1/CIP1）是细胞周期的负调节因子，尽管它的表达是由一些促进细胞增殖的有丝分裂原诱导的。我们发现E2F1和E2F3这两种转录因子可以激活细胞周期进程所需的基因，它们是p21启动子的强激活因子。相比之下，HBP1 （HMG-box蛋白-1）是一种新的视网膜母细胞瘤蛋白结合蛋白，可以抑制p21启动子并抑制E2F对p21表达的诱导，E2F和HBP1都通过位于p21启动子-119至+ 16核苷酸之间的顺式作用元件调节p21的转录，这些蛋白的DNA结合域都是活性所必需的。-119和-60碱基对之间的序列包含4个Spl共识元件和2个非规范E2F结合位点，对E2F的激活至关重要，尽管E2F1和E2F3在该片段被删除时激活表达的能力程度不同。E2Fs和HBP1对p21启动子活性的相反作用表明，这些因素之间的相互作用可能决定了体内p21的转录水平。
The Cdk inhibitor p21(WAF1/CIP1) is a negative regulator of the cell cycle, although its expression is induced by a number of mitogens that promote cell proliferation. We have found that E2F1 and E2F3, transcription factors that activate genes required for cell cycle progression, are strong activators of the p21 promoter. In contrast, HBP1 (HMG-box protein-1), a novel retinoblastoma protein-binding protein, can repress the p21 promoter and inhibit induction of p21 expression by E2F, Both E2Fs and HBP1 regulate p21 transcription through cis-acting elements located between nucleotides -119 to + 16 of the p21 promoter and the DNA binding domains of each of these proteins are required for activity. Sequences between -119 and -60 basepairs containing four Spl consensus elements and two noncanonical E2F binding sites are of major importance for E2F activation, although E2F1 and E2F3 differ in the extent of their ability to activate expression when this segment is deleted. The opposing effects of E2Fs and HBP1 on p21 promoter activity suggest that interplay between these factors may determine the level of p21 transcription in vivo.