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人类wig-1,一种p53靶基因,编码一种生长抑制性锌指蛋白。

Human wig-1, a p53 target gene that encodes a growth inhibitory zinc finger protein.

作者信息

Hellborg F, Qian W, Mendez-Vidal C, Asker C, Kost-Alimova M, Wilhelm M, Imreh S, Wiman K G

机构信息

Department of Oncology-Pathology, Cancer Center Karolinska (CCK), Karolinska Institute, SE-171 76 Stockholm, Sweden.

出版信息

Oncogene. 2001 Sep 6;20(39):5466-74. doi: 10.1038/sj.onc.1204722.

Abstract

We previously identified a novel p53-induced mouse gene, wig-1, that encodes a 290 amino acid zinc finger protein (Varmeh-Ziaie et al., 1997). Here we have identified and characterized the human homolog of mouse wig-1. The human wig-1 protein is 87% identical to the mouse protein and contains three zinc finger domains and a putative nuclear localization signal. Human wig-1 mRNA and protein is induced following activation of wild type p53 expression in our BL41-ts p53 Burkitt lymphoma cells. Wig-1 is also induced in MCF7 cells following treatment with the DNA-damaging agent mitomycin C. Northern blotting detected low levels of wig-1 mRNA in normal human tissues. Fluorescence in situ hybridization mapped wig-1 to human chromosome 3q26.3-27. FLAG-tagged human wig-1 localizes to the nucleus. Ectopic overexpression of human wig-1 inhibits tumor cell growth in a colony formation assay. These results suggest that human wig-1 has a role in the p53-dependent growth regulatory pathway.

摘要

我们之前鉴定出一个新的p53诱导的小鼠基因wig-1,它编码一个含290个氨基酸的锌指蛋白(Varmeh-Ziaie等人,1997年)。在此,我们鉴定并表征了小鼠wig-1的人类同源物。人类wig-1蛋白与小鼠蛋白的同源性为87%,包含三个锌指结构域和一个假定的核定位信号。在我们的BL41-ts p53伯基特淋巴瘤细胞中,野生型p53表达激活后,人类wig-1 mRNA和蛋白被诱导表达。在用DNA损伤剂丝裂霉素C处理MCF7细胞后,wig-1也被诱导表达。Northern印迹法检测到wig-1 mRNA在正常人体组织中的表达水平较低。荧光原位杂交将wig-1定位于人类染色体3q26.3-27。带有FLAG标签的人类wig-1定位于细胞核。在集落形成试验中,人类wig-1的异位过表达抑制肿瘤细胞生长。这些结果表明,人类wig-1在p53依赖的生长调节途径中发挥作用。

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