ZNF424，一种新型人类 KRAB/C2H2 锌指蛋白，抑制 NFAT 和 p21 通路。

ZNF424, a novel human KRAB/C2H2 zinc finger protein, suppresses NFAT and p21 pathway.

机构信息

The Center for Heart Development, College of Life Sciences, Hunan Normal University, Changsha, 410081 Hunan, P. R. of China.

出版信息

BMB Rep. 2010 Mar;43(3):212-8. doi: 10.5483/bmbrep.2010.43.3.212.

DOI:10.5483/bmbrep.2010.43.3.212

PMID:20356463

Abstract

Zinc finger-containing transcription factors are the largest single family of transcriptional regulators in mammals, which play an essential role in cell differentiation, cell proliferation, apoptosis, and neoplastic transformation. Here we have cloned a novel KRAB-related zinc finger gene, ZNF424, encoding a protein of 555aa. ZNF424 gene consisted of 4 exons and 3 introns, and mapped to chromosome 19p13.3. ZNF424 gene was ubiquitously expressed in human embryo tissues by Northern blot analysis. ZNF424 is conserved across species in evolution. Using a GFP-labeled ZNF424 protein, we demonstrate that ZNF424 localizes mostly in the nucleus. Transcriptional activity assays shows ZNF424 suppresses transcriptional activity of L8G5-luciferase. Overexpression of ZNF424 in HEK- 293 cells inhibited the transcriptional activity of NFAT and p21, which may be silenced by siRNA. The results suggest that ZNF424 protein may act as a transcriptional repressor that suppresses NFAT and p21 pathway to mediate cellular functions.

摘要

锌指转录因子是哺乳动物中转录调控因子最大的一个家族，它们在细胞分化、细胞增殖、细胞凋亡和肿瘤转化中起着至关重要的作用。在这里，我们克隆了一个新的 KRAB 相关锌指基因 ZNF424，它编码一个 555 个氨基酸的蛋白质。ZNF424 基因由 4 个外显子和 3 个内含子组成，定位于染色体 19p13.3。通过 Northern blot 分析，发现 ZNF424 基因在人胚胎组织中广泛表达。ZNF424 在进化上是跨物种保守的。利用 GFP 标记的 ZNF424 蛋白，我们证明 ZNF424 主要定位于细胞核内。转录活性测定显示 ZNF424 抑制 L8G5-荧光素酶的转录活性。在 HEK-293 细胞中过表达 ZNF424 抑制 NFAT 和 p21 的转录活性，这可能被 siRNA 沉默。这些结果表明，ZNF424 蛋白可能作为一种转录抑制因子，通过抑制 NFAT 和 p21 通路来调节细胞功能。