Nguyên-Nhu Nhu Tiên, Berck Jehanne, Clippe André, Duconseille Elee, Cherif Hanane, Boone Christophe, Van der Eecken Valérie, Bernard Alfred, Banmeyer Ingrid, Knoops Bernard
Laboratory of Cell Biology, ISV, Department of Biology, Université catholique de Louvain, Place Croix du Sud 5, B-1348 Louvain-la-Neuve, Belgium.
Biochim Biophys Acta. 2007 Jul-Aug;1769(7-8):472-83. doi: 10.1016/j.bbaexp.2007.05.004. Epub 2007 Jun 2.
Peroxiredoxin 5 (PRDX5) is a mammalian thioredoxin peroxidase ubiquitously expressed in tissues. Its role as antioxidant enzyme has been previously supported in different pathological situations. In this study, we determined the complete human PRDX5 genomic organization and isolated the 5'-flanking region of the gene. Human PRDX5 gene is composed of six exons and five introns similarly to other chordate PRDX5 genes. Several single nucleotide polymorphisms were identified. Six out of them have amino acid substitutions in protein-coding region. Analysis of the 5'-flanking region of human PRDX5 revealed the presence of a TATA-less promoter containing a canonical CpG island and several putative response elements for transcription factors. To analyze the regulatory mechanisms controlling human PRDX5 expression, we characterized the 5'-flanking region by cloning various segments of this region in front of a luciferase reporter sequence. Transfection in HepG2 cells indicate that the 5'-flanking region contains regulatory elements for constitutive expression of human PRDX5. Multiple transcription start sites were also identified by 5'-RACE-PCR in human liver. Moreover, although no corresponding proteins were reported, we present new alternative splicing variants encoded specifically by human PRDX5 gene. The characterization of human PRDX5 gene revealed the complexity of its regulation and a high variability of sequences that might be associated with pathological situations.
过氧化物酶体增殖物激活受体5（PRDX5）是一种在组织中普遍表达的哺乳动物硫氧还蛋白过氧化物酶。先前在不同病理情况下已证实其作为抗氧化酶的作用。在本研究中，我们确定了完整的人类PRDX5基因组织结构，并分离出该基因的5'侧翼区域。人类PRDX5基因由六个外显子和五个内含子组成，与其他脊索动物的PRDX5基因相似。鉴定出了几个单核苷酸多态性。其中六个在蛋白质编码区有氨基酸替换。对人类PRDX5 5'侧翼区域的分析表明，存在一个无TATA盒的启动子，其中包含一个典型的CpG岛和几个假定的转录因子反应元件。为了分析控制人类PRDX5表达的调控机制，我们通过在荧光素酶报告序列前克隆该区域的各个片段来表征5'侧翼区域。在HepG2细胞中的转染表明，5'侧翼区域包含人类PRDX5组成型表达的调控元件。通过5'-RACE-PCR在人肝脏中也鉴定出了多个转录起始位点。此外，尽管没有报道相应的蛋白质，但我们展示了由人类PRDX5基因特异性编码的新的可变剪接变体。人类PRDX5基因的表征揭示了其调控的复杂性以及可能与病理情况相关的序列的高度变异性。
