Tumor suppressive effect of lysyl oxidase proenzyme

• Published in: Biochimica et biophysica acta Vol. 1793; no. 7; pp. 1272 - 1278
• Main Authors: Contente, Sara, Yeh, Tze-Jou Annie, Friedman, Robert M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2009
• Subjects: Animals; Antibody; Cell Line, Transformed; Embryo, Mammalian - cytology; Embryo, Mammalian - enzymology; Enzyme Precursors - metabolism; Fibroblasts - cytology; Fibroblasts - enzymology; Immunoblotting; Interferon; Lysyl oxidase; Mice; NIH 3T3 Cells; Peptide Fragments - immunology; Protein Biosynthesis; Protein-Lysine 6-Oxidase - metabolism; RNA interference; Transcription, Genetic; Tumor suppressor; Tumor Suppressor Proteins - metabolism; Interferon; RNA interference; Lysyl oxidase; Antibody; Tumor suppressor
• ISSN: 0167-4889; 0006-3002; 1879-2596; 1878-2434
• DOI: 10.1016/j.bbamcr.2009.04.013

Lysyl oxidase acts as both a matrix modifying enzyme and an oncogene suppressor. It is synthesized as a 50-kDa proenzyme, secreted, and processed into an ∼30 kDa mature, active enzyme and an 18-kDa propeptide. The tumor suppressive effect of lysyl oxidase appears to be exerted within the cell, so the subcellular localization of protein forms was investigated. Propeptide-specific antibody detected 50-kDa proenzyme in cytoplasmic and nuclear extracts of non-transformed mouse fibroblasts, but free 18-kDa propeptide was not detected in any extract. Antibody to epitope near the N-terminus of mature lysyl oxidase detected the proenzyme product in non-transformed cells, and a 30-kDa cytoplasmic protein in both non-transformed and transformed cells. RNA interference reduced the expression of lysyl oxidase mRNA and 50-kDa proenzyme in non-transformed cells, but had no effect on 30-kDa protein, indicating that although this protein displays a lysyl oxidase epitope, it is not derived from lysyl oxidase message. The absence of both free 18-kDa propeptide and mature lysyl oxidase within non-transformed cells suggests that cellular reversion after restoration of lysyl oxidase gene expression is mediated by the 50-kDa proenzyme within cells.