The regulation of the p53/MDM2 feedback loop by microRNAs.
The regulation of the p53/MDM2 feedback loop by microRNAs.
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DOI：
10.14800/rd.502
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Feng Z
中科院分区：
文献类型：
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作者：
Zhang C;Liu J;Wang X;Feng Z
抑癌基因p53及其信号通路在肿瘤预防中起着重要作用。E3泛素连接酶MDM 2是p53的直接转录靶点，也是p53最关键的负调节因子，它与细胞中的p53形成一个自动调节负反馈环，以紧密调节p53的水平和活性。microRNA（miRNAs）是一类内源性表达的非编码小RNA，在基因表达的翻译后调控中起着重要作用。最近的研究表明，miRNAs直接调节p53或MDM 2的水平，从而调节p53在肿瘤抑制中的功能。最近，我们鉴定了一种新的miRNA miR-339- 5 p，其直接抑制MDM 2以激活p53并增强p53在肿瘤抑制中的功能。因此，miRNAs通过调节p53/MDM 2反馈环成为p53信号通路的一个新的但重要的组成部分。
Tumor suppressor p53 and its signaling pathway play a central role in tumor prevention. The E3 ubiquitin ligase MDM2, which is a direct p53 transcriptional target and also the most critical negative regulator of p53, forms an autoregulatory negative feedback loop with p53 in the cell to tightly regulate the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that play a critical role in the post-translational regulation of gene expression. Recent studies have revealed that miRNAs directly regulate the levels of p53 or MDM2 to modulate the p53 function in tumor suppression. Recently, we identified miR-339-5p as a new miRNA that directly represses MDM2 to activate p53 and enhance p53 function in tumor suppression. Thus, miRNAs have become a new but important component of the p53 signaling pathway through regulating the p53/MDM2 feedback loop.