TRANSFORMING GROWTH-FACTOR BETA(1)-MEDIATED INDUCTION OF JUNB IS SELECTIVELY INHIBITED BY EXPRESSION OF AD.12-E1A

Transforming growth factor beta (TGF-beta), a multifunctional polypeptide growth factor, regulates the expression of many genes critical to cell cycle progression, such as members of the jun gene family which encode components of the transcription factor complex AP-1. The transforming proteins encoded by the early region 1A of adenovirus12 (Ad.12-E1A) abrogate some of the cellular responses to TGF-beta as well as affecting, differentially, the expression of cellular jun genes. Our data demonstrate that expression of Ad.12-E1A in rat 3Y1 fibroblast cells inhibits induction of junB by TGF-beta(1) while not altering the regulation of junB by phorbol ester or serum. Regulation of c-jun gene expression by TGF-beta(1), phorbol ester, and serum is not appreciably altered by the expression of Ad.l2-E1A. Inhibition of TGF-beta induced junB expression is not due to a defect in TGF-beta/receptor interaction on Ad.12-E1A transformed cells and is not observed in other isotypic fibroblast cells transformed by SV40 or polyomavirus. These data suggest that multiple, independent, intracellular signal transduction pathways exist which mediate genomic responses to TGF-beta. Cellular expression of Ad.12-E1A-12S gene products results in selective disruption of some TGF-beta(1) signaling cascades and not those activated by phorbol ester or serum. These data further suggest that some cellular targets which mediate TGF-beta(1) action may also be unique targets of action for the E1A-12S transforming protein of adenovirus12. (C) 1994 Wiley-Liss, Inc.