ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway
ZNF418, a novel human KRAB/C2H2 zinc finger protein, suppresses MAPK signaling pathway
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ZNF418，一种新型人 KRAB/C2H2 锌指蛋白，抑制 MAPK 信号通路
DOI：
10.1007/s11010-007-9674-4
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发表时间：
2008-03-01
影响因子：
4.3
通讯作者：
Wu, Xiushan
中科院分区：
文献类型：
--
作者：
Li, Yongqing;Yang, Dan;Wu, Xiushan
心脏分化涉及一系列协调的基因表达，以确定的时空方式调节细胞增殖和基质蛋白的形成。含有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，并且被认为对人类心脏发育和疾病很重要。在这里，我们从人类胚胎心脏cDNA文库中鉴定并表征了一个新的锌指基因znf418。该基因位于染色体19q13.43上，全长13.5 kb，包含6个外显子，转录全长3.7 kb的mRNA，编码含有676个氨基酸残基的蛋白质。预测的蛋白包含一个KRAB-A盒和17个串联C2H2型锌指基序。Northern blot分析表明，znf418在多个胎儿和成人组织中表达，但在心脏中表达水平较高。报告基因分析表明，ZNF418是一个转录抑制因子，其KRAB基序代表基础抑制域。在COS-7细胞中过表达ZNF418可抑制SRE和AP-1的转录活性，这些转录活性可能被siRNA沉默。这些结果表明，ZNF418是锌指转录因子家族的成员，可能在MAPK信号通路中起负调控作用。
Cardiac differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporal-spatial manner. Zinc finger-containing transcription factors have been implicated as critical regulators of multiple cardiac-expressed genes, and are thought to be important for human heart development and diseases. Here, we have identified and characterized a novel zinc finger gene namedZNF418from a human embryo heart cDNA library. The gene spans 13.5 kb on chromosome 19q13.43 encompassing six exons, and transcribes a 3.7-kb mRNA that encodes a protein with 676 amino acid residues. The predicted protein contains a KRAB-A box and 17 tandem C2H2 type zinc finger motifs. Northern blot analysis indicates thatZNF418is expressed in multiple fetal and adult tissues, but is expressed at higher levels in the heart. Reporter gene assays show that ZNF418 is a transcriptional repressor, and the KRAB motif of ZNF418 represents the basal repressive domain. Overexpression of ZNF418 in COS-7 cells inhibits the transcriptional activity of SRE and AP-1 which may be silenced by siRNA. These results suggest that ZNF418 is a member of the zincfinger transcription factor family and may act as a negative regulator in MAPK signaling pathway.