Huang Chunxia, Wang Yuequn, Li Dali, Li Yongqing, Luo Jian, Yuan Wuzhou, Ou Ying, Zhu Chuanbing, Zhang Yuejuan, Wang Zhi, Liu Mingyao, Wu Xiushan
The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, PR China.
Biochem Biophys Res Commun. 2004 Aug 6;320(4):1298-305. doi: 10.1016/j.bbrc.2004.06.080.
Zinc finger proteins play important roles in a variety of cellular functions, including cell growth, proliferation, apoptosis, and intracellular signal transduction, and the zinc finger-containing transcription factor has been implicated as a critical regulator of multiple cardiac-expressed genes as well as a regulator of inducible gene expression in response to hypertrophic stimulation. With the aim of identifying the genes involved in human heart development and diseases, we have isolated a novel LER-related zinc finger gene named ZNF394 from human heart cDNA library. ZNF394 gene has a predicted 561-amino acid open reading frame, encoding a 64kDa zinc finger protein. The N-terminus of ZNF394 protein has a leucine-rich region (LER or SCAN domain), followed by a well-conserved krüppel-associated box domain. The C-terminus of the protein contains 7 C2H2 zinc finger motifs in tandem arrays with the highly conserved space region of the H/C-link. ZNF394 gene is mapped to chromosome 7q11.21. Northern blot analysis indicates that a 2.18kb transcript specific for ZNF394 is specifically expressed in the heart, skeletal muscle, and brain in human adult tissues. ZNF394 protein is expressed in cell nucleus. Overexpression of ZNF394 in the cell inhibits the transcriptional activities of c-Jun and AP-1 reporters, suggesting that ZNF394 is a new transcriptional repressor in mitogen-activated protein kinase signaling pathways and may play an important role in cardiac development and/or cardiac function.
锌指蛋白在多种细胞功能中发挥重要作用，包括细胞生长、增殖、凋亡和细胞内信号转导，含锌指的转录因子被认为是多种心脏表达基因的关键调节因子，也是对肥厚性刺激作出反应的诱导基因表达的调节因子。为了鉴定参与人类心脏发育和疾病的基因，我们从人类心脏cDNA文库中分离出一个新的与LER相关的锌指基因，命名为ZNF394。ZNF394基因有一个预测的561个氨基酸的开放阅读框，编码一个64kDa的锌指蛋白。ZNF394蛋白的N端有一个富含亮氨酸的区域（LER或SCAN结构域），随后是一个高度保守的krüppel相关盒结构域。该蛋白的C端包含7个串联排列的C2H2锌指基序，具有高度保守的H/C连接空间区域。ZNF394基因定位于染色体7q11.21。Northern印迹分析表明，一个2.18kb的ZNF394特异性转录本在人类成人组织的心脏、骨骼肌和大脑中特异性表达。ZNF394蛋白在细胞核中表达。ZNF394在细胞中的过表达抑制了c-Jun和AP-1报告基因的转录活性，表明ZNF394是丝裂原活化蛋白激酶信号通路中的一种新的转录抑制因子，可能在心脏发育和/或心脏功能中发挥重要作用。
