Abstract
Lysyl oxidase (EC 1.4.3.13) is a copper-dependent enzyme acting principally on collagen and elastin catalyzing the formation of aldehyde cross-links. It is also believed to possess a tumor suppressor activity as the anti-oncogene of ras. While rat, human, and mouse lysyl oxidase cDNAs have been cloned, little is known about the structure of the gene, its organization, or regulation. This paper describes the cloning of an intronic segment of the human lysyl oxidase gene. Sequence analysis defined the location of an intron that separates the prepro-coding segments from the segment encoding the catalytic domain. Genomic restriction mapping and gene copy number data established that multiple lysyl oxidase mRNA transcripts originate from a single gene and thus are products of alternative splicing. Northern analysis of adult and fetal fibroblast RNA showed a dominant approximately 4.3-kilobase lysyl oxidase mRNA transcript that varied in abundance as a function of cell line. These data are consistent with a complex mechanism regulating the expression of the lysyl oxidase gene.
Highlights
Lysyloxidase has been characterized to varying degrees from several speciesand sources of tissue
(1).The current understandinogf its properties and functionsprimary substrates, elastin andcollagen, have been described have recently been summarized [2]. It is a copper-dependent [15,16,17], comparatively little isknown about the organization enzyme thatcatalyzes the formation of aldehyde cross-links, of the lysyl oxidase gene or the origin of the multiple lysyl acting primarily on elastin ancodllagen
Northern analysis from adult and fetal fibroblast RNAs suggests that the expression of the lysyl oxidase gene is subject to complex modes of regulation and may be subject to developmental regulation
Summary
)I Supported by a March of Dimes predoctoral fellowship. Miniprint is easilyreadwith the aid of a standard magnifying glass. Full size photocopies are included in the microfilm. ** To whom reprint requests shouldbe addressed: Dept. Of Molec- edition of the Journal thatis available from Waverly Press. The abbreviationsused are: PCR, polymerase chain reaction; bp, cine, 540 E. Tel.: 313-577-0765; base pair(s); FIGE, field inversion gel electrophoresis;kb,kilobase
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