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ZNF322是一种新型人类C2H2型克鲁ppel样锌指蛋白,可调节丝裂原活化蛋白激酶(MAPK)信号通路中的转录激活。

ZNF322, a novel human C2H2 Kruppel-like zinc-finger protein, regulates transcriptional activation in MAPK signaling pathways.

作者信息

Li Yongqing, Wang Yuequn, Zhang Caibo, Yuan Wuzhou, Wang Jun, Zhu Chuanbing, Chen Lei, Huang Wen, Zeng Weiqi, Wu Xiushan, Liu Mingyao

机构信息

The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, Peoples' Republic of China.

出版信息

Biochem Biophys Res Commun. 2004 Dec 24;325(4):1383-92. doi: 10.1016/j.bbrc.2004.10.183.

Abstract

Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. The C(2)H(2) zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes and are important for human heart development and diseases. Here we have identified and characterized a novel zinc-finger gene named ZNF322 using degenerated primers from a human embryo heart cDNA library. The gene contains four exons and spans 23.2kb in chromosome 6p22.1 region, and transcribes a 2.7kb mRNA that encodes a protein with 402 amino acid residues. The predicted protein contains 9 tandem C(2)H(2)-type zinc-finger motifs. Northern blot analysis shows that ZNF322 is expressed in every human tissue examined at adult stage and during embryonic developmental stages from 80 days to 24 weeks. When overexpressed in COS-7 cells, ZNF322-EGFP fusion protein is detected in the nucleus and cytoplasm. Reporter gene assays show that ZNF322 is a transcriptional activator. Furthermore, overexpression of ZNF322 in COS-7 cells activates the transcriptional activity of SRE and AP-1. Together, these results suggest that ZNF322 is a member of the zinc-finger transcription factor family and may act as a positive regulator in gene transcription mediated by the MAPK signaling pathways.

摘要

心脏分化涉及一系列协调的基因表达,这些表达以特定的时空方式调节细胞增殖和基质蛋白形成。含C(2)H(2)锌指的转录因子被认为是多个心脏表达基因的关键调节因子,对人类心脏发育和疾病很重要。在此,我们使用来自人类胚胎心脏cDNA文库的简并引物鉴定并表征了一个名为ZNF322的新型锌指基因。该基因包含四个外显子,跨越6号染色体p22.1区域的23.2kb,转录出一个2.7kb的mRNA,编码一个含有402个氨基酸残基的蛋白质。预测的蛋白质包含9个串联的C(2)H(2)型锌指基序。Northern印迹分析表明,ZNF322在成年期以及80天至24周的胚胎发育阶段所检测的每个人类组织中均有表达。当在COS-7细胞中过表达时,在细胞核和细胞质中检测到ZNF322-EGFP融合蛋白。报告基因检测表明ZNF322是一种转录激活因子。此外,ZNF322在COS-7细胞中的过表达激活了SRE和AP-1的转录活性。总之,这些结果表明ZNF322是锌指转录因子家族的成员,可能在MAPK信号通路介导的基因转录中作为正调节因子发挥作用。

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