Actin: a novel interaction partner of WT1 influencing its cell dynamic properties
Actin: a novel interaction partner of WT1 influencing its cell dynamic properties
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DOI：
10.1038/onc.2009.444
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发表时间：
2010-02-18
期刊：
影响因子：
8
通讯作者：
Hastie, N.
中科院分区：
文献类型：
--
作者：
Dudnakova, T.;Spraggon, L.;Hastie, N.
Wilms 肿瘤抑制因子 WT1 是一种锌指蛋白，在泌尿生殖系统的正常发育和肿瘤发生中发挥着关键作用。 WT1 的突变或缺失会导致儿童出现一系列发育障碍和对肾母细胞瘤的易感性。与致癌功能相关的 Wt1 异位表达已在大量恶性肿瘤中观察到，包括血液癌和实体癌。尽管 Wt1 在正常组织中主要是核蛋白，但在大多数表达 Wt1 的肿瘤中它主要是细胞质。在这项研究中，肌动蛋白被鉴定为细胞核和细胞质中新的 WT1 相互作用伙伴。我们在体外和体内证实了这种相互作用，并开始探索其功能意义。肌动蛋白细胞骨架的扰动使 Wt1 从细胞质中的多核糖体部分移出，取消了其核质穿梭并改变了 Wt1 DNA 和 RNA 结合能力。这些数据对 Wt1 与 RNA 代谢相关的功能以及对癌细胞中细胞骨架变化的反应具有影响。因此，我们的研究结果可以更多地阐明这两种蛋白质的功能，并可能为新癌症疗法的开发铺平道路。癌基因 (2010) 29, 1085-1092; doi：10.1038/onc.2009.444； 2009 年 12 月 7 日在线发布
The Wilms' tumour suppressor, WT1, is a zinc finger protein with key roles in normal development of the genitourinary system and tumourigenesis. Mutations or deletion of WT1 result in a spectrum of developmental disorders and susceptibility to Wilms' tumour in children. Ectopic expression of Wt1 associated with oncogenic functions has been observed in a large number of malignancies, including haematological and solid cancers. Although Wt1 is predominantly a nuclear protein in normal tissues, it is mostly cytoplasmic in the majority of Wt1-expressing tumours. Actin was identified in this study as a new WT1 interaction partner both in the nucleus and in the cytoplasm. We confirmed this interaction both in vitro and in vivo and started to explore its functional significance. Perturbation of the actin cytoskeleton moved Wt1 off the polysome fraction in the cytoplasm, cancelled its nucleo-cytoplasmic shuttling and altered Wt1 DNA- and RNA-binding abilities. These data have implications for Wt1 functions in relation to RNA metabolism and response to cytoskeletal alterations in cancer cells. Thus, our findings could shed more light on the functions of both these proteins and possibly pave way for the development of new cancer therapies. Oncogene (2010) 29, 1085-1092; doi:10.1038/onc.2009.444; published online 7 December 2009