Alternative promoter activation leads to the expression of a novel human lysyl oxidase variant that functions as an amine oxidase
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.
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Document Type: Research Article
Affiliations: Department of Biochemistry, Wonkwang University School of Medicine, Iksan, Jeollabuk-Do 570-749, Republic of Korea
Publication date: January 1, 2014
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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