TRANSFORMING GROWTH-FACTOR-BETA-1 ENHANCES SERUM-INDUCED DEPHOSPHORYLATION OF THE P53 PROTEIN IN CELL-LINES GROWTH-INHIBITED BY THIS FACTOR

A 24 hr TGF-beta 1 treatment (4 ng/ml) of SV40-transformed WI38 embryo nic fibroblasts (VA13 cells) causes a moderate but reproducible inhibi tion of their serum-stimulated growth. By immunoprecipitation with the PAb122 antibody, we show that serum stimulation of previously serum-d eprived cells causes a dephosphorylation of the wild type P53 protein, which is accentuated by the TGF-beta 1 treatment. The TGF-beta 1-enha nced dephosphorylation effect is also observed in two other cell lines growth-inhibited by TGF-beta 1, but which do not contain Large T (min k lung CCL64 and human KHOS cells). On the contrary, TGF-beta 1 treatm ent of the untransformed WI38 fibroblasts stimulates their growth, wit hout affecting the phosphorylation of P53. Such treatment did not affe ct the expression of the corresponding mRNA nor the level of synthesis of the protein. The results suggest that the P53 protein could be a d ownstream target of TGF-beta 1 action on those cells growth-inhibited by the factor.