POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1
POZ domain transcription factor, FBI-1, represses transcription of ADH5/FDH by interacting with the zinc finger and interfering with DNA binding activity of Sp1
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DOI：
10.1074/jbc.m202078200
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发表时间：
2002-07-26
影响因子：
4.8
通讯作者：
Hur, MW
中科院分区：
文献类型：
--
作者：
Lee, DK;Suh, D;Hur, MW
POZ结构域是在许多转录因子中发现的蛋白-蛋白相互作用基序，对发育、肿瘤发生、细胞凋亡和转录抑制都很重要。我们克隆了POZ结构域转录因子FBI-1，该转录因子在体外和体内均能识别ADH5/FDH最小启动子（bp -38 ~ +61） Sp1核心结合位点（bp -22 ~ +22）上游的顺式元件（bp -38 ~ -22）。ADH5/FDH最小启动子被FBI-1有效抑制。谷胱甘肽s -转移酶融合蛋白下拉表明，FBI-1、Plzf和Bel-6的POZ结构域直接与Sp1的锌指DNA结合结构域相互作用。dna酶I足迹分析表明，这种相互作用阻止了Spl与ADH5/FDH启动子GC盒的结合。针对GC盒近端的Gal4- poz结构域融合抑制了Gal4上游激活子序列sp1 -腺病毒主要晚期启动子的转录。我们的数据表明，POZ结构域通过与Sp1锌指相互作用和干扰Sp1的DNA结合活性来抑制转录。
The POZ domain is a protein-protein interaction motif that is found in many transcription factors, which are important for development, oncogenesis, apoptosis, and transcription repression. We cloned the POZ domain transcription factor, FBI-1, that recognizes the cis-element (bp -38 to -22) located just upstream of the core Sp1 binding sites (bp -22 to +22) of the ADH5/FDH minimal promoter (bp -38 to +61) in vitro and in vivo, as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The ADH5/FDH minimal promoter is potently repressed by the FBI-1. Glutathione S-transferase fusion protein pull-down showed that the POZ domains of FBI-1, Plzf, and Bel-6 directly interact with the zinc finger DNA binding domain of Sp1. DNase I footprinting assays showed that the interaction prevents binding of Spl to the GC boxes of the ADH5/FDH promoter. Gal4-POZ domain fusions targeted proximal to the GC boxes repress transcription of the Gal4 upstream activator sequence-Sp1-adenovirus major late promoter. Our data suggest that POZ domain represses transcription by interacting with Sp1 zinc fingers and by interfering with the DNA binding activity of Sp1.