Decreased retinoylation in NIH 3T3 cells transformed with activated Ha-ras.
Retinoylation (retinoic acid acylation) is a post-translation modification of proteins occurring in a variety of mammalian cell lines and in vivo. To gain further knowledge of the role of retinoylation we studied it in NIH 3T3 cells and NIH 3T3 cells transformed by an activated Ha-ras oncogene (NIH Ha-ras-3T3 cells). In serum-free medium retinoic acid (RA) inhibited growth of NIH 3T3 cells but did not inhibit growth of NIH Ha-ras-3T3 cells. After incubation with [3H]RA, the level of retinoylated protein in NIH 3T3 cells was about 1.5-fold greater than in NIH Ha-ras-3T3 cells. On one-dimensional polyacrylamide gel electrophoresis, both the rate and the extent of retinoylation were greater in NIH 3T3 cells. We detected about 40 retinoylated proteins in NIH 3T3 cells by two-dimensional polyacrylamide gel electrophoresis. Only about 15 proteins were retinoylated, but at reduced levels, in NIH Ha-ras-3T3 cells. These results suggest that the activated ras oncogene inhibits retinoylation. This inhibition may in turn be related to the loss of other RA responses of NIH 3T3 cells, including growth inhibition, retinoic acid catabolism, down-regulation of fibronectin biosynthesis, and induction of tissue-type transglutaminase, which are not seen to the same extent in NIH Ha-ras-3T3 cells.
Takahashi
N
N
Department of Health Chemistry, Hoshi University, Tokyo, Japan.
De Luca
L M
LM
Breitman
T R
TR
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005353:Fibronectins / Q000096:biosynthesis; D020558:GTP Phosphohydrolases / Q000096:biosynthesis; D019204:GTP-Binding Proteins; D011905:Genes, ras; D051379:Mice; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000096:biosynthesis; D014212:Tretinoin / Q000378:metabolism*
D005353:Fibronectins; D014212:Tretinoin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins