Interaction and functional cooperation of NF-kappa B with Smads - Transcriptional regulation of the junB promoter

The transforming growth factor-beta (TGF-beta) family of cytokines regulate s diverse cellular processes through control of the expression of target ge nes. Smad proteins are a recently identified family of signal transducers f or members of the TGF-beta family. Smads act as transcriptional regulators through binding to DNA and interacting with a variety of transcription fact ors. Here, we identified a ICE Site as a TGF-beta-responsive region in the 3'-downstream junB promoter region. We also demonstrate that kappa B sites alone are sufficient to mediate immediate transcriptional activation by TGF -beta. Transactivation of kappa B Sites by TGF-beta requires an intact NF-k appa B pathway, cooperates with known activators of this pathway, and is me diated by Smad family members. Furthermore, we show that Smads interacts wi th p52 in vivo. These data expand the model in which Smad proteins undergo multiple interactions with several transcription factors that could induce either activation or repression of gene expression.