Anti-proliferative Effect of C3 Exoenzyme in Fibroblasts is Mediated by c-Jun Phosphorylation.

ABSTRACT: The ADP-ribosyltransferase C3 exoenzyme from C. botulinum selectively inactivates Rho and is therefore often used as an inhibitor for investigations on Rho signaling. Previous studies of our group revealed that C3 inhibited cell proliferation in HT22 cells accompanied by increased transcriptional activities of Sp1 and c-Jun and reduced levels of cyclin D1, p21 and phosphorylated p38. By use of a p38?-deficient and a p38?-expressing control cell line, the impact of p38 on C3-mediated inhibition of cell proliferation and alterations on MAPK signaling was studied by growth kinetic experiments and Western blot analyses. The cell growth of p38?-expressing cells was impaired by C3, while the p38?-deficient cells did not exhibit any C3-induced effect. The activity of the MKK3/6-p38 MAPK signaling cascade as well as the phosphorylation of c-Jun and JNK was reduced by C3 exclusively in the presence of p38?. Moreover, the activity of upstream MAPKKK TAK1 was lowered in the p38?-expressing cells. These results indicated a resistance of p38?-deficient cells to C3-mediated inhibition of cell growth. This anti-proliferative effect was highly associated with the decreased activity of c-Jun and upstream p38 and JNK MAPK signaling as a consequence of the absence of p38? in these cells.

SUBMITTER: von Elsner L 

PROVIDER: S-EPMC5630077 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature