Zik1, a transcriptional repressor that interacts with the heterogeneous nuclear ribonucleoprotein particle K protein
Zik1, a transcriptional repressor that interacts with the heterogeneous nuclear ribonucleoprotein particle K protein
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DOI：
10.1074/jbc.271.44.27701
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发表时间：
1996-11-01
影响因子：
4.8
通讯作者：
Bomsztyk, K
中科院分区：
文献类型：
--
作者：
Denisenko, ON;ONeill, B;Bomsztyk, K
异质核核糖核蛋白颗粒（hnRNP） K蛋白由多个模块结构域组成，这些结构域用于参与多种分子伙伴，包括DNA， RNA，原癌基因vav的产物以及酪氨酸和丝氨酸/苏氨酸激酶。为了鉴定更多的K蛋白分子伙伴并进一步了解其功能，我们在酵母双杂交筛选中使用K蛋白片段作为诱饵。其中一个阳性克隆的初级结构显示了一个新的锌指蛋白，特此记为Zik1。除了在C端有9个相邻的锌指外，Zik1含有一个被认为参与转录抑制的KRAB-A结构域，在体外，Zik1和K蛋白结合，并从细胞提取物中共免疫沉淀，这表明它们在体内是直接相互作用的。Gal4 DNA结合域-Zik1融合蛋白的表达抑制了带有Gal4结合元件的基因启动子，表明同源DNA元件Zik1是转录抑制因子。已知的K蛋白分子相互作用的多样性，以及现在对K蛋白伙伴转录抑制因子的鉴定，支持了K蛋白是一个非常通用的分子的概念，它可能作为一个对接平台，促进参与信号转导和基因表达的分子之间的交流。
The heterogeneous nuclear ribonucleoprotein particle (hnRNP) K protein is comprised of multiple modular domains that serve to engage a diverse group of molecular partners including DNA, RNA, the product of the proto-oncogene vav, and tyrosine and serine/threonine kinases. To identify additional K protein molecular partners and to further understand its function, we used a fragment of K protein as a bait in the yeast two-hybrid screen. The deduced primary structure of one of the positive clones revealed a novel zinc finger protein, hereby denoted as Zik1. In addition to the nine contiguous zinc fingers in the C terminus, Zik1 contains a KRAB-A domain thought to be involved in transcriptional repression, Zik1 and K protein bound in vitro and co-immunoprecipitated from cell extracts indicating that in vivo their interaction is direct. Expression of Gal4 DNA-binding domain-Zik1 fusion protein repressed a gene promoter bearing Gal4-binding elements, indicating that from cognate DNA elements Zik1 is a transcriptional repressor. The known diverse nature of K protein molecular interactions and now the identification of a K protein partner that is a transcriptional repressor lends support to the notion that K protein is a remarkably versatile molecule that may be acting as a docking platform to facilitate communication among molecules involved in signal transduction and gene expression.