IDENTITY OF GABP WITH NRF-2, A MULTISUBUNIT ACTIVATOR OF CYTOCHROME-OXIDASE EXPRESSION, REVEALS A CELLULAR ROLE FOR AN ETS DOMAIN ACTIVATOR OF VIRAL PROMOTERS
IDENTITY OF GABP WITH NRF-2, A MULTISUBUNIT ACTIVATOR OF CYTOCHROME-OXIDASE EXPRESSION, REVEALS A CELLULAR ROLE FOR AN ETS DOMAIN ACTIVATOR OF VIRAL PROMOTERS
复制标题
DOI：
10.1101/gad.7.3.380
复制
发表时间：
1993-03-01
影响因子：
10.5
通讯作者：
SCARPULLA, RC
中科院分区：
文献类型：
--
作者：
VIRBASIUS, JV;VIRBASIUS, CMA;SCARPULLA, RC
ETS结构域蛋白是一个不同的转录激活因子家族，最近已经涉及许多细胞特异性和病毒启动子的表达。核呼吸因子2（NRF-2）是一种核转录因子，通过串联序列元件激活大鼠细胞色素c氧化酶亚基IV（RCO 4）基因的近端启动子。这些元件符合高亲和力ETS结构域识别位点的共识。我们现在已经从HeLa细胞中纯化了NRF-2，并发现它由五种多肽组成，其中只有一种具有内在的DNA结合能力。其他参与形成具有不同结合特性的异聚复合物。NRF-2还特异性识别小鼠细胞色素c氧化酶亚基Vb（MCO 5 b）基因中的多个结合位点。与功能相关的RCO 4基因一样，串联排列的NRF-2位点对近端MCO 5 b启动子的活性至关重要，进一步证实了NRF-2在呼吸链表达中的作用。从HeLa NRF-2的各种亚基的肽序列的测定揭示了高度的序列同一性与小鼠GA结合蛋白（GABP），多亚基ETS结构域激活剂的单纯疱疹病毒立即早期基因。因此，细胞在激活指定线粒体呼吸功能的核基因中的作用被分配给病毒启动子的ETS结构域激活剂。
The ETS domain proteins are a diverse family of transcriptional activators that have been implicated recently in the expression of a number of cell-specific and viral promoters. Nuclear respiratory factor 2 (NRF-2) is a nuclear transcription factor that activates the proximal promoter of the rat cytochrome c oxidase subunit IV (RCO4) gene through tandem sequence elements. These elements conform to the consensus for high-affinity ETS domain recognition sites. We have now purified NRF-2 to homogeneity from HeLa cells and find that it consists of five polypeptides, only one of which has intrinsic DNA-binding ability. The others participate in the formation of heteromeric complexes with distinct binding properties. NRF-2 also specifically recognizes multiple binding sites in the mouse cytochrome c oxidase subunit Vb (MCO5b) gene. As in the functionally related RCO4 gene, tandemly arranged NRF-2 sites are essential for the activity of the proximal MCO5b promoter, further substantiating a role for NRF-2 in respiratory chain expression. Determination of peptide sequences from the various subunits of HeLa NRF-2 reveals a high degree of sequence identity with mouse GA-binding protein (GABP), a multisubunit ETS domain activator of herpes simplex virus immediate early genes. A cellular role in the activation of nuclear genes specifying mitochondrial respiratory function is thus assigned to an ETS domain activator of viral promoters.