Kritzik M R, Ziober A F, Dicharry S, Conrad D J, Sigal E
Institute of Biochemistry and Cell Biology, Syntex Discovery Research, Palo Alto, CA, USA.
Biochim Biophys Acta. 1997 Jun 26;1352(3):267-81. doi: 10.1016/s0167-4781(97)00005-5.
15-lipoxygenase is a lipid-peroxidating enzyme that oxidizes fatty acids, such as those esterified to cellular membranes. It has been implicated in the oxidative modification of low-density lipoprotein and is thus thought to contribute to the development of atherosclerosis. The enzyme has also been shown to be specifically induced by interleukin-4 in human blood monocytes. Two 15-lipoxygenase-hybridizing messages were detected in these cells; one (2.7 kb) corresponds to the previously isolated cDNA for 15-lipoxygenase, while the other (4 kb) was of unknown origin. We have isolated and characterized this 4 kb transcript. Our experiments show that it has 1.2 kb additional sequence in its 3' untranslated region, and that it is generated from genomic sequences through differential polyA site selection. We present studies to address the functional significance of the extended 3'UTR. Selection of an upstream polyadenylation signal results in production of the 2.7 kb transcript. In addition, we present here for the first time the cloning and sequence of the human 15-lipoxygenase gene, as well as the identification of regulatory elements in the promoter region of this gene.
15-脂氧合酶是一种脂质过氧化酶，可氧化脂肪酸，如那些酯化到细胞膜上的脂肪酸。它与低密度脂蛋白的氧化修饰有关，因此被认为有助于动脉粥样硬化的发展。该酶还被证明在人血单核细胞中可被白细胞介素-4特异性诱导。在这些细胞中检测到两种与15-脂氧合酶杂交的信使RNA；一种（2.7 kb）对应于先前分离的15-脂氧合酶的cDNA，而另一种（4 kb）来源不明。我们已经分离并鉴定了这个4 kb的转录本。我们的实验表明，它在其3'非翻译区有1.2 kb的额外序列，并且它是通过差异聚腺苷酸化位点选择从基因组序列产生的。我们进行了研究以探讨延长的3'非翻译区的功能意义。选择上游聚腺苷酸化信号会导致产生2.7 kb的转录本。此外，我们首次在此展示了人15-脂氧合酶基因的克隆和序列，以及该基因启动子区域调控元件的鉴定。
