SIP1, a novel zinc finger homeodomain repressor, interacts with Smad proteins and binds to 5′-CACCT sequences in candidate target genes
SIP1, a novel zinc finger homeodomain repressor, interacts with Smad proteins and binds to 5′-CACCT sequences in candidate target genes
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DOI：
10.1074/jbc.274.29.20489
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发表时间：
1999-07-16
影响因子：
4.8
通讯作者：
Huylebroeck, D
中科院分区：
文献类型：
--
作者：
Verschueren, K;Remacle, JE;Huylebroeck, D
转化生长因子β受体的激活导致Smad蛋白的磷酸化和核转位，进而参与靶基因表达的调节。我们描述了一种新的Smad相互作用蛋白SIP1，它是通过酵母双杂交系统鉴定出来的。虽然SIP1在酵母和体外与受体调节的Smads的MH2结构域相互作用，但在哺乳动物细胞中它与全长Smads的相互作用需要受体介导的Smad激活。SIP1是双手锌指/同源域Delta EF1/ZFH-1家族的新成员。与Delta EF1一样，SIP1在不同的启动子中与5‘-CACCT序列结合，包括短爪猴的启动子。在体外与Xbra2启动子结合的全长SIP1或其C端锌指簇的过表达阻止了内源Xbra基因在非洲爪哇早期胚胎中的表达。因此，SIP1和Delta EF1一样，可能是一个转录抑制因子，可能参与至少一个激活素依赖的信号转导途径的即时反应基因的调节。这种Smad相互作用蛋白的发现为研究转化生长因子β成员在反应细胞和脊椎动物胚胎中影响靶基因表达的机制开辟了新的途径。
Activation of transforming growth factor beta receptors causes the phosphorylation and nuclear translocation of Smad proteins, which then participate in the regulation of expression of target genes. We describe a novel Smad-interacting protein, SIP1, which was identified using the yeast two-hybrid system. Although SIP1 interacts with the MH2 domain of receptor-regulated Smads in yeast and in vitro, its interaction with full length Smads in mammalian cells requires receptor-mediated Smad activation. SIP1 is a new member of the delta EF1/Zfh-1 family of two-handed zinc finger/homeodomain proteins. Like delta EF1, SIP1 binds to 5'-CACCT sequences in different promoters, including the Xenopus brachyury promoter. Overexpression of either full-length SIP1 or its C-terminal zinc finger cluster, which bind to the Xbra2 promoter in vitro, prevented expression of the endogenous Xbra gene in early Xenopus embryos. Therefore, SIP1, like delta EF1, is likely to be a transcriptional repressor, which may be involved in the regulation of at least one immediate response gene for activin-depend ent signal transduction pathways. The identification of this Smad-interacting protein opens new routes to investigate the mechanisms by which transforming growth factor beta members exert their effects on expression of target genes in responsive cells and in the vertebrate embryo.