Wan X S, Devalaraja M N, St Clair D K
Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0054, USA.
DNA Cell Biol. 1994 Nov;13(11):1127-36. doi: 10.1089/dna.1994.13.1127.
Human manganese superoxide dismutase (MnSOD) is one of the major cellular defense enzymes that protects against toxic effects of superoxide radicals. Overexpression of human MnSOD has been shown to inhibit radiation-induced neoplastic transformation, suppress malignancy of cancer cells, and increase tolerance to various toxic agents. To elucidate the human MnSOD gene structure for identification of potential regulatory elements, we isolated five lambda clones from a normal human genomic DNA library and sequenced the largest clone containing the entire human MnSOD gene. The results demonstrated that human MnSOD is a single-copy gene consisting of five exons interrupted by four introns with typical splice junctions. A distinctive transcription initiation site was identified 74 bp upstream from the translation start site. This transcription initiation site is preceded by a G + C-rich (78%) promoter region containing a cluster of seven SP1 and three AP2 consensus sequences with no TATA box or CAAT box. The 3'-flanking region of the MnSOD gene contains one NF-kappa B consensus sequence. The presence of SP1, AP2, and NF-kappa B consensus sequences suggests that these potential regulatory elements may play a role in the regulation of human MnSOD gene expression.
人锰超氧化物歧化酶（MnSOD）是主要的细胞防御酶之一，可抵御超氧阴离子自由基的毒性作用。人MnSOD的过表达已被证明可抑制辐射诱导的肿瘤转化、抑制癌细胞的恶性程度并提高对各种有毒物质的耐受性。为了阐明人MnSOD基因结构以鉴定潜在的调控元件，我们从正常人基因组DNA文库中分离出5个λ克隆，并对包含整个人MnSOD基因的最大克隆进行了测序。结果表明，人MnSOD是一个单拷贝基因，由5个外显子组成，被4个内含子打断，具有典型的剪接接头。在翻译起始位点上游74 bp处鉴定出一个独特的转录起始位点。该转录起始位点之前是一个富含G + C（78%）的启动子区域，包含一组7个SP1和3个AP2共有序列，没有TATA盒或CAAT盒。MnSOD基因的3'侧翼区域包含一个NF-κB共有序列。SP1、AP2和NF-κB共有序列的存在表明这些潜在的调控元件可能在人MnSOD基因表达的调控中发挥作用。
