p53 binds selectively to the 5′ untranslated region of cdk4, an RNA element necessary and sufficient for transforming growth factor β- and p53-mediated translational inhibition of cdk4
p53 binds selectively to the 5′ untranslated region of cdk4, an RNA element necessary and sufficient for transforming growth factor β- and p53-mediated translational inhibition of cdk4
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DOI：
10.1128/mcb.20.22.8420-8431.2000
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发表时间：
2000-11-01
影响因子：
5.3
通讯作者：
Ewen, ME
中科院分区：
文献类型：
--
作者：
Miller, SJ;Suthiphongchai, T;Ewen, ME
转化生长因子β治疗的一个结果是抑制CDK4的合成，这依赖于P53。在这里，我们证明了CDK4mRNA的5‘非翻译区是野生型p53依赖的转化生长因子-β调节的CDK4翻译抑制的必要条件和充分条件。野生型P53选择性地与CDK4mRNA的5‘非编码区结合，并抑制含有该区域的RNA的翻译。RNA结合和翻译控制是P53基因上可分离的两个功能，特异性和非特异性RNA结合也是如此。此外，P53的反式激活缺陷突变保留了调节CDK4翻译的能力。我们的发现表明，在体内，P53在对转化生长因子-β的反应中起着翻译调节的作用。
One consequence of transforming growth factor beta (TGF-beta) treatment is inhibition of Cdk4 synthesis, and this is dependent on p53. Here, we show that the 5' untranslated region (UTR) of the cdk4 mRNA is both necessary and sufficient for wild-type p53-dependent TGF-beta -regulated translational inhibition of cdk4. Wild-type p53 bound selectively to the 5' UTR of the cdk4 mRNA and inhibited translation of RNAs that contain this region. RNA binding and translational control are two genetically separable functions of p53, as are specific and nonspecific RNA binding. Moreover, transactivation-defective mutants of p53 retain the ability to regulate cdk4 translation. Our findings suggest that p53 functions as a regulator of translation in response to TGF-beta in vivo.