The MDM2-p53 pathway: multiple roles in kidney development.
The MDM2-p53 pathway: multiple roles in kidney development.
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DOI：
10.1007/s00467-013-2629-y
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发表时间：
2014-04
影响因子：
3
通讯作者：
Saifudeen, Zubaida
中科院分区：
文献类型：
--
作者：
El-Dahr, Samir S.;Hilliard, Sylvia;Aboudehen, Karam;Saifudeen, Zubaida
肾单位祖细胞更新和分化为新生上皮肾单位的分子基础是一个深入研究的领域。这些早期阶段的缺陷导致肾发育不全，最终导致高血压和慢性肾脏疾病。终末肾单位分化，即肾上皮前体细胞退出细胞周期并获得生理功能的过程同样重要。终末上皮细胞分化失败导致肾发育不良和膀胱形成。因此，更好地了解调控早期和晚期肾细胞分化的转录框架具有重要的临床意义。在这篇综述中，我们将讨论的证据表明，MDM 2-p53通路在细胞命运的决定在发展过程中。从功能丧失和获得研究中出现的中心主题是，p53水平和转录活性的严格调控是肾发生绝对需要的。我们还将讨论p53的翻译后修饰（例如，乙酰化和磷酸化）改变p53的时空和功能性质，从而改变肾发育期间的细胞命运。Mdm 2-p53通路中的突变和多态性存在于超过50%的人类癌症中。这就提出了一个问题，即Mdm 2-p53通路中的序列变异是否会增加对肾发育不全、高血压或慢性肾脏疾病的易感性。随着全外显子组测序和其他高通量技术的出现，这一假设在肾发育不全儿童队列中得到了验证。
The molecular basis of nephron progenitor cell renewal and differentiation into nascent epithelial nephrons is an area of intense investigation. Defects in these early stages of nephrogenesis lead to renal hypoplasia, and eventually hypertension and chronic kidney disease. Terminal nephron differentiation, the process by which renal epithelial precursors cells exit the cell cycle and acquire physiological functions is equally important. Failure of terminal epithelial cell differentiation results in renal dysplasia and cystogenesis. Thus, a better understanding of the transcriptional frameworks which regulate early and late renal cell differentiation is of great clinical significance. In this review, we will discuss evidence implicating the Mdm2-p53 pathway in cell fate determination during development. The emerging central theme from loss- and gain-of-function studies is that tight regulation of p53 levels and transcriptional activity is absolutely required for nephrogenesis. We will also discuss how post-translational modifications of p53 (e.g., acetylation and phosphorylation) alter the spatiotemporal and functional properties of p53 and thus cell fate during kidney development. Mutations and polymorphisms in the Mdm2-p53 pathway are present in more than 50% of cancers in humans. This raises the question of whether sequence variants in the Mdm2-p53 pathway increase the susceptibility to renal dysgenesis, hypertension or chronic kidney disease. With the advent of whole exome sequencing and other high throughput technologies, this hypothesis is testable in cohorts of children with renal dysgenesis.
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影响因子：
8
作者：
Allemand, I;Anglo, A;May, E
通讯作者：
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