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一种新的含KRAB结构域的人类锌指基因ZNF446可抑制SRE和AP-1的转录活性。

A novel human KRAB-containing zinc-finger gene ZNF446 inhibits transcriptional activities of SRE and AP-1.

作者信息

Liu Fang, Zhu Chuanbing, Xiao Jing, Wang Yuequn, Tang Wenxian, Yuan Wuzhou, Zhao Yulian, Li Yongqing, Xiang Zhiming, Wu Xiushan, Liu Mingyao

机构信息

The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, People's Republic of China.

出版信息

Biochem Biophys Res Commun. 2005 Jul 22;333(1):5-13. doi: 10.1016/j.bbrc.2005.05.069.

DOI:10.1016/j.bbrc.2005.05.069
PMID:15936718
Abstract

Kruppel-related zinc-finger proteins constitute the largest individual family of transcription factors in mammals [C. Looman, L. Hellman, M. Abrink, A novel Kruppel-associated box identified in a panel of mammalian zinc-finger proteins, Mammalian Genome 15 (1) (2004) 35-40.[1]]. Here we identified and characterized a novel zinc-finger gene named ZNF446. The predicted protein contains a KRAB and three C(2)H(2) zinc fingers. Northern blot analysis shows that ZNF446 is expressed in a variety of human adult tissues with the highest expression level in muscle. ZNF446 is a transcription repressor when fused to GAL4 DNA-binding domain and co-transfected with VP-16. Overexpression of ZNF446 in COS-7 cells inhibits the transcriptional activities of SRE and AP-1, in which the KRAB motif represents the basal transcriptional repressive activity, suggesting that the ZNF446 protein may act as a transcriptional repressor in mitogen-activated protein kinase (MAPK) signaling pathway to mediate cellular functions.

摘要

与克鲁ppel相关的锌指蛋白构成了哺乳动物中转录因子的最大单一家族[C. 洛曼、L. 赫尔曼、M. 阿布林克,在一组哺乳动物锌指蛋白中鉴定出一种新型克鲁ppel相关框,《哺乳动物基因组》15 (1) (2004) 35 - 40。[1]]。在此,我们鉴定并表征了一个名为ZNF446的新型锌指基因。预测的蛋白质包含一个KRAB和三个C(2)H(2)锌指。Northern印迹分析表明,ZNF446在多种人类成人组织中表达,在肌肉中的表达水平最高。当与GAL4 DNA结合结构域融合并与VP - 16共转染时,ZNF446是一种转录抑制因子。ZNF446在COS - 7细胞中的过表达抑制了SRE和AP - 1的转录活性,其中KRAB基序代表基础转录抑制活性,这表明ZNF446蛋白可能在丝裂原活化蛋白激酶(MAPK)信号通路中作为转录抑制因子来介导细胞功能。

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