CHARACTERIZATION AND SEQUENCE OF AN ADDITIONAL 15-LIPOXYGENASE TRANSCRIPT AND OF THE HUMAN GENE

15-lipoxygenase is a lipid-peroxidating enzyme that oxidizes fatty aci ds, such as those esterified to cellular membranes. It has been implic ated in the oxidative modification of low-density lipoprotein and is t hus thought to contribute to the development of atherosclerosis. The e nzyme has also been shown to be specifically induced by interleukin-4 in human blood monocytes. Two 15-lipoxygenase-hybridizing messages wer e detected in these cells; one (2.7 kb) corresponds to the previously isolated cDNA for 15-lipoxygenase, while the other (4 kb) was of unkno wn origin. We have isolated and characterized this 4 kb transcript. Ou r experiments show that it has 1.2 kb additional sequence in its 3' un translated region, and that it is generated from genomic sequences thr ough differential polyA site selection. We present studies to address the functional significance of the extended 3'UTR. Selection of an ups tream polyadenylation signal results in production of the 2.7 kb trans cript. In addition, we present here for the first time the cloning and sequence of the human 15-lipoxygenase gene, as well as the identifica tion of regulatory elements in the promoter region of this gene. (C) 1 997 Elsevier Science B.V. All rights reserved. (C) 1997 Elsevier Scien ce B.V.