ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5′UTR
ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5′UTR
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DOI：
10.1101/gad.248902
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发表时间：
2002-12-01
影响因子：
10.5
通讯作者：
Hengst, L
中科院分区：
文献类型：
--
作者：
Kullmann, M;Göpfert, U;Hengst, L
p27（Kip1）通过结合和抑制细胞周期蛋白依赖性激酶抑制细胞增殖。为了研究p27的翻译调控机制，我们分离了一个完整的p27 cDNA，并在其5'UTR中鉴定了一个内部核糖体进入位点（IRES）。IRES允许在帽相关翻译减少的条件下进行有效的p27翻译。为了寻找IRES活性的可能调节因子，我们已经确定神经元ELAV蛋白HuD是p27 5'UTR的特定结合因子。HuD表达增加或普遍表达的HuR蛋白特异性抑制p27翻译和p27 IRES活性。与Hu蛋白在p27翻译中的抑制作用一致，siRNA介导的HuR敲低可诱导内源性p27蛋白水平以及ires介导的报告基因翻译，并导致G1期细胞周期阻滞。
p27(Kip1) restrains cell proliferation by binding to and inhibiting cyclin-dependent kinases. To investigate the mechanisms of p27 translational regulation, we isolated a complete p27 cDNA and identified an internal ribosomal entry site (IRES) located in its 5'UTR. The IRES allows for efficient p27 translation under conditions where cap-dependent translation is reduced. Searching for possible regulators of IRES activity we have identified the neuronal ELAV protein HuD as a specific binding factor of the p27 5'UTR. Increased expression of HuD or the ubiquitously expressed HuR protein specifically inhibits p27 translation and p27 IRES activity. Consistent with an inhibitory role of Hu proteins in p27 translation, siRNA mediated knockdown of HuR induced endogenous p27 protein levels as well as IRES-mediated reporter translation and leads to cell cycle arrest in G1.