Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence.
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.
Saito
H
H
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-0643, USA. hsaito@marlin.utmb.edu
Papaconstantinou
J
J
Sato
H
H
Goldstein
S
S
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion; D016922:Cellular Senescence; D018076:DNA, Complementary / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D008249:Protein-Lysine 6-Oxidase / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D014898:Werner Syndrome / Q000235:genetics*
D018076:DNA, Complementary; D012333:RNA, Messenger; D008249:Protein-Lysine 6-Oxidase