Department of Haematology and Transfusion Medicine, Lund University, Lund, Sweden.
Eur J Haematol. 2018 Mar;100(3):229-240. doi: 10.1111/ejh.13010. Epub 2018 Jan 10.
The Wilms' tumour gene 1 protein (WT1) is a zinc finger transcription factor found indispensable for foetal development. WT1 has also been implicated in the development of tumours in several organ systems, including acute myeloid leukaemia (AML). Four main WT1 isoforms come from 2 alternative splice events. One alternative splice results in the inclusion or exclusion of 3 amino acids, KTS, between zinc fingers 3 and 4 in the WT1 protein. The KTS insert has been extensively investigated due to the functional implications for DNA and RNA binding. In this review, we provide an overview of the research into the isoforms containing or lacking the KTS insert in leukaemic cells, as well as the research into the binding patterns of the WT1 -KTS and +KTS isoforms to DNA and RNA. Finally, we connect the results of the DNA binding research to the ChIP-CHIP and ChIP-Seq investigations into the global genomic binding of the WT1 protein that have recently been performed.
Wilms 瘤基因 1 蛋白(WT1)是一种锌指转录因子,对于胎儿发育是不可或缺的。WT1 也与包括急性髓细胞性白血病(AML)在内的多个器官系统的肿瘤发生有关。WT1 有 4 种主要的异构体,来自 2 种选择性剪接事件。一种选择性剪接导致 WT1 蛋白的锌指 3 和 4 之间插入或缺失 3 个氨基酸,KTS。由于对 DNA 和 RNA 结合的功能影响,KTS 插入已被广泛研究。在这篇综述中,我们概述了在白血病细胞中含有或缺乏 KTS 插入的异构体的研究,以及 WT1-KTS 和+KTS 异构体与 DNA 和 RNA 结合模式的研究。最后,我们将 DNA 结合研究的结果与最近进行的 WT1 蛋白全基因组结合的 ChIP-CHIP 和 ChIP-Seq 研究联系起来。