Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence

Abstract

We report here a novel cDNA clone with a predicted protein sequence similar to lysyl oxidase. This full-length cDNA clone of 3432 base pairs (WS9-14) was isolated from human fibroblasts on the basis of its overexpression in senescent cells. It encodes an 87-kDa polypeptide, whose protein is a member of the scavenger receptor cysteine-rich family, because it contains four scavenger receptor cysteine-rich domains that are found in several secreted or cell surface proteins. The WS9-14 protein has a 48% identity with both lysyl oxidase and lysyl oxidase-like protein at a region corresponding to exons 2-6, implying the existence of a lysyl oxidase gene family. The pattern of WS9-14 gene expression by fibroblasts parallels pro-collagen I-alpha1 expression. Its mRNA level is induced by transforming growth factor beta-1 and indomethacin and inhibited by phorbol ester and retinoic acid. WS9-14 is abundantly expressed in all tumor cell lines examined that attach to culture dishes but not in cell lines that grow in suspension and is also up-regulated in senescent fibroblasts. These results suggest that WS9-14 gene encodes an extracellular protein that may be specifically involved in cell adhesion and senescence.