Mrowka C, Schedl A
Max Delbrück Center for Molecular Medicine, Humboldt University of Berlin, Berlin-Buch, Germany.
J Am Soc Nephrol. 2000 Nov;11 Suppl 16:S106-15.
Normal development of the kidney is a highly complex process that requires precise orchestration of proliferation, differentiation, and apoptosis. In the past few years, a number of genes that regulate these processes, and hence play pivotal roles in kidney development, have been identified. The Wilms' tumor suppressor gene WT1 has been shown to be one of these essential regulators of kidney development, and mutations in this gene result in the formation of tumors and developmental abnormalities such as the Denys-Drash and Frasier syndromes. A fascinating aspect of the WT1 gene is the multitude of isoforms produced from its genomic locus. In this review, our current understanding of the structural features of WT1, how they modulate the transcriptional and post-transcriptional activities of the protein, and how mutations affecting individual isoforms can lead to diseased kidneys is summarized. In addition, results from transgenic experiments, which have yielded important findings regarding the function of WT1 in vivo, are discussed. Finally, data on the unusual feature of RNA editing of WT1 transcripts are presented, and the relevance of RNA editing for the normal functioning of the WT1 protein in the kidney is discussed.
肾脏的正常发育是一个高度复杂的过程，需要精确协调细胞增殖、分化和凋亡。在过去几年中，已经鉴定出许多调节这些过程并因此在肾脏发育中起关键作用的基因。肾母细胞瘤抑制基因WT1已被证明是肾脏发育的这些重要调节因子之一，该基因的突变会导致肿瘤形成和发育异常，如Denys-Drash综合征和Frasier综合征。WT1基因的一个引人入胜的方面是其基因组位点产生的多种异构体。在这篇综述中，总结了我们目前对WT1结构特征的理解，它们如何调节蛋白质的转录和转录后活性，以及影响单个异构体的突变如何导致肾脏疾病。此外，还讨论了转基因实验的结果，这些实验产生了关于WT1在体内功能的重要发现。最后，展示了关于WT1转录本RNA编辑异常特征的数据，并讨论了RNA编辑与WT1蛋白在肾脏中正常功能的相关性。
