title: Alternative promoter activation leads to the expression of a novel human lysyl oxidase variant that functions as an amine oxidase.
abstract: The lysyl oxidase (LOX) family is an emerging family of amine oxidases that is responsible for lysine-mediated crosslinks found in collagen and elastin. Several novel functions, such as tumor suppression, tumor progression, cellular senescence, chemotaxis and the modification of histones have recently been attributed to the LOX family of proteins. In the search for more human LOX paralogs, in the present study, we identified several expressed sequence tag (EST) clones that showed an alternative exon-intron splice pattern from LOX. These ESTs corresponded to the LOX transcript variant 2 (LOX-v2) that was recently reported in GenBank (accession no. NM_001178102). LOX-v2 mRNA lacks exon 1 of LOX, but contains an additional 222 bp sequence from the 5'-flanking intronic region of exon 2. The deduced LOX-v2 polypeptide contains the characteristic C-terminal domains of the LOX family, but does not contain the N-terminal propeptide region that has been reported to have tumor suppressor activity. In peroxidase-coupled fluorometric assays, LOX-v2 showed β-aminopropionitrile-inhibitable amine oxidase activity toward collagen and elastin. RT-PCR analysis of human tissues revealed a distinct tissue specificity of LOX-v2 expression compared to that of LOX. Promoter assays indicated that an alternative promoter element present in the exon 1 region of LOX was sufficient for the differential expression of LOX-v2. These findings indicate that the human LOX gene encodes 2 variants, LOX and LOX-v2, both of which function as amine oxidases with distinct tissue specificities.
authors.affiliation: Department of Biochemistry, Wonkwang University School of Medicine, Iksan, Jeollabuk-Do 570-749, Republic of Korea.
authors.forename: Seonkwan
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Wonkwang University School of Medicine, Iksan, Jeollabuk-Do 570-749, Republic of Korea.
authors.forename: Sunhyang
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Wonkwang University School of Medicine, Iksan, Jeollabuk-Do 570-749, Republic of Korea.
authors.forename: Youngho
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000378:metabolism*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D008249:Protein-Lysine 6-Oxidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D008249:Protein-Lysine 6-Oxidase; D008995:Monoamine Oxidase