Nuclear respiratory factor 1 activation sites in genes encoding the gamma-subunit of ATP synthase, eukaryotic initiation factor 2 alpha, and tyrosine aminotransferase. Specific interaction of purified NRF-1 with multiple target genes.
Nuclear respiratory factor 1 activation sites in genes encoding the gamma-subunit of ATP synthase, eukaryotic initiation factor 2 alpha, and tyrosine aminotransferase. Specific interaction of purified NRF-1 with multiple target genes.
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DOI：
10.1016/s0021-9258(19)50527-0
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发表时间：
1992-04
期刊：
影响因子：
--
通讯作者：
Ching Man A Chau;M. J. Evans;R. Scarpulla
中科院分区：
文献类型：
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作者：
Ching Man A Chau;M. J. Evans;R. Scarpulla
转录因子核呼吸因子1（NRF-1）最初被鉴定为细胞色素c基因的激活剂，随后发现通过其产物在线粒体中起作用的其他核基因中的特定位点刺激转录。这些包括细胞色素氧化酶和还原酶复合物的亚基和线粒体DNA复制机制的组成部分。在这里，我们建立了NRF-1的功能识别位点存在于ATP合酶γ亚基基因中，将NRF-1的拟议呼吸作用扩展到复合物V。此外，在编码真核翻译起始因子2 α亚基和酪氨酸氨基转移酶的基因中发现了具有生物活性的NRF-1位点，它们都参与蛋白质生物合成和酪氨酸催化剂的各自途径的限速步骤。来自这些基因中的每一个的识别位点与NRF-1形成相同的复合物，如通过竞争结合测定、甲基化干扰足迹和UV诱导的DNA交联所建立的。每个NRF-1结合位点的克隆寡聚体也刺激转染细胞中截短的细胞色素c启动子的活性。NRF-1对各个靶位点的结合活性共纯化约33，000倍，并存在于68 kDa的单个蛋白质中。这些观察结果进一步支持了NRF-1在核呼吸基因表达中的作用，并表明它可能有助于协调呼吸代谢与其他生物合成和降解途径。
Transcription factor nuclear respiratory factor 1 (NRF-1) was originally identified as an activator of the cytochrome c gene and subsequently found to stimulate transcription through specific sites in other nuclear genes whose products function in the mitochondria. These include subunits of the cytochrome oxidase and reductase complexes and a component of the mitochondrial DNA replication machinery. Here we establish that a functional recognition site for NRF-1 is present in the ATP synthase gamma-subunit gene extending the proposed respiratory role of NRF-1 to complex V. In addition, biologically active NRF-1 sites are found in genes encoding the eukaryotic translation initiation factor 2 alpha-subunit and tyrosine aminotransferase, both of which participate in the rate-limiting step of their respective pathways of protein biosynthesis and tyrosine catabolism. The recognition sites from each of these genes form identical complexes with NRF-1 as established by competition binding assays, methylation interference footprinting, and UV-induced DNA cross-linking. Cloned oligomers of each NRF-1 binding site also stimulate the activity of a truncated cytochrome c promoter in transfected cells. The NRF-1 binding activities for the various target sites copurified approximately 33,000-fold and resided in a single protein of 68 kDa. These observations further support a role for NRF-1 in the expression of nuclear respiratory genes and suggest it may help coordinate respiratory metabolism with other biosynthetic and degradative pathways.