Regulation of collagen post-translational modification in transformed human and chick-embryo cells.
Changes in the regulation of collagen post-translational modification in transformed cells were studied in three established human sarcoma cell lines and in chick-embryo fibroblasts freshly transformed by Rous sarcoma virus. The collagens synthesized by all but one of these and by all the control human and chick-embryo cell lines were almost exclusively of types I and/or III. The relative rate of collagen synthesis and the amounts of prolyl hydroxylase activity and immunoreactive protein were markedly low in all the transformed human cell lines. The other enzymes studied, lysyl hydroxylase, hydroxylysyl galactosyltransferase and galactosylhydroxylysyl glucosyltransferase, never showed as large a decrease in activity as did prolyl hydroxylase, suggesting a more efficient regulation of the last enzyme than of the three others. The chick-embryo fibroblasts freshly transformed by Rous sarcoma virus differed from the human sarcoma cells in that prolyl hydroxylase activity was distinctly increased, whereas the decreases in immunoreactive prolyl hydroxylase protein and the three other enzyme activities were very similar to those in the simian-virus-40-transformed human fibroblasts. It seems possible that this increased prolyl hydroxylase activity is only a temporary phenomenon occurring shortly after the transformation, and may be followed by a decrease in activity later. The newly synthesized collagens of all the transformed cells that produced almost exclusively collagen types I and/or III had high extents of lysyl hydroxylation, and there was also an increase in the ratio of glycosylated to non-glycosylated hydroxylysine. The data suggest that one critical factor affecting modification is the rate of collagen synthesis, which affects the ratio of enzyme to substrate in the cell.
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D002642:Chick Embryo; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D005700:Galactosyltransferases / Q000378:metabolism; D005964:Glucosyltransferases / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D006901:Hydroxylysine / Q000378:metabolism; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D014176:Protein Biosynthesis; D012513:Sarcoma, Experimental / Q000201:enzymology / Q000378:metabolism*
D006901:Hydroxylysine; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D005700:Galactosyltransferases; D005964:Glucosyltransferases; C023236:UDPgalactose-collagen galactosyltransferase; C023247:UDP glucose-collagen glucosyltransferase