부산대학교 도서관

Smad proteins transduce signals from TGF-[besa] receptors and regulate transcription of target genes either directly or in combination with other sequence-specific transcription factors. AP-1 sites and their cognate transcription factors also play important roles in the gene regulatory activities of TGF-[besa]. In this report, we have investigated the functional interactions of the Smad and AP-1 transcription factors. We demonstrate that Smad and AP-1 complexes specifically bind to their cognate cis-elements and do not interact with each other on-DNA, whereas off-DNA interactions occur between Smad3 and both c-Jun and JunB. Using both artificial constructs specific for either the Smad or AP-1 signaling pathways or natural promoters known to be TGF-[besa]-responsive, we have determined that Jun family members downregulate Smad3-mediated gene transactivation whereas AP-1-dependent promoters are synergistically activated by Smad3 and Jun proteins. We propose a model where the presence of Smad- and/or AP-1-specific cis-elements within TGF-[besa]-responsive genes allows dynamic modulation of gene expression, in contrast to the existing model where interactions between Smad and AP-1 proteins are merely an on/off mechanism to regulate TGF-[besa]/Smad targets. Oncogene(2001) 20,3332-3340. Keywords: TGF-[besa], AP-1, Smad, gene regulation, Jun
Author(s): Franck Verrecchia [1]; Laurence Vindevoghel [2]; Robert J Lechleider [3]; Jouni Uitto [2]; Anita B Roberts [3]; Alain Mauviel [1, 2] Introduction Cellular signaling from the TGF-[besa] family of [...]