STRUCTURE OF THE HUMAN CYCLO-OXYGENASE-2 GENE
STRUCTURE OF THE HUMAN CYCLO-OXYGENASE-2 GENE
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DOI：
10.1042/bj3020723
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发表时间：
1994-09-15
影响因子：
4.1
通讯作者：
HLA, T
中科院分区：
文献类型：
--
作者：
APPLEBY, SB;RISTIMAKI, A;HLA, T
环氧合酶(COX)是前列腺素合成的限速酶，由COX-1和COX-2两个基因编码，这两个基因的表达和调控存在差异。人COX-1和COX-2多肽具有61%的初级序列同源性。COX-1在静止期细胞中的表达最高，而COX-2的表达受生长因子和细胞因子的诱导。我们用人COX-2(hCOX-2)基因5‘-非翻译区(UTR)的一个探针筛选了一个人基因组文库，并分离了两个重叠的基因组克隆。我们已经测定了转录起始点上游0.8kb的DNA序列，6kb的蛋白质编码区，包括10个外显子和9个内含子，以及2.5kb的3‘-非编码区。HCOX-1和hCOX-2以及小鼠TIS10(COX-2)基因的结构高度保守，但有少数例外。COX-1和COX-2的3‘-UTRs。基因是不同的；例如，COX-2基因中最大的外显子编码整个3‘-UTR，包含22个拷贝的AUUA’RNA不稳定元件。5‘-侧翼区的序列分析显示了几个潜在的转录调控序列，包括一个TATA盒，一个C/EBP基序，两个AP-2位点，三个SP1位点，两个NF-kappa B位点，一个Cre基序和一个Ets-1位点。这些工作为进一步研究COX-2基因转录和转录后调控机制奠定了基础。
Cyclo-oxygenase (Cox), a rate-limiting enzyme in the synthesis of prostanoids, is encoded by two genes, Cox-1 and Cox-2, which are differentially expressed and regulated. Human Cox-1 and -2 polypeptides share 61% primary sequence identity. While the expression of Cox-1 is maximal in quiescent cells, Cox-2 expression is induced by growth factors and cytokines, We have screened a human genomic library with a probe from the 5'-untranslated region (UTR) of the human Cox-2 (hCox-2) cDNA and isolated two overlapping genomic clones. We have determined the DNA sequence of 0.8 kb upstream of the transcription start site, 6 kb of protein coding region, which includes 10 exons and 9 introns, as well as 2.5 kb of the 3'-UTR. The structures of the hCox-1 and hCox-2 and the murine TIS10 (Cox-2) genes are highly conserved, with a few exceptions. The 3'-UTRs of the Cox-1 and -2. genes are distinct; for example, the largest exon in the Cox-2 gene encodes the entire 3'-UTR, containing 22 copies of the AUUUA' RNA instability element. Sequence analysis of the 5'-flanking region has shown several potential transcription regulatory sequences, including a TATA box, a C/EBP motif, two AP-2 sites, three SP1 sites, two NF-kappa B sites, a CRE motif and an Ets-1 site. These efforts serve as a basis for future studies on transcriptional and post-transcriptional mechanisms of Cox-2 gene regulation.