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J. Biol. Chem., Vol. 275, Issue 37, 28937-28946, September 15, 2000

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Interaction and Functional Cooperation of NF-B with Smads
TRANSCRIPTIONAL REGULATION OF THE junB PROMOTER^*

Teresa López-Rovira, Elisabet Chalaux^§, Jose Luis Rosa, Ramon Bartrons, and Francesc Ventura^¶

From the Departament de Ciències Fisiològiques II, Campus de Bellvitge, Universitat de Barcelona, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Spain

The transforming growth factor (TGF) family of cytokines regulates diverse cellular processes through control of the expression of target genes. Smad proteins are a recently identified family of signal transducers for members of the TGF family. Smads act as transcriptional regulators through binding to DNA and interacting with a variety of transcription factors. Here, we identified a B site as a TGF--responsive region in the 3'-downstream junB promoter region. We also demonstrate that B sites alone are sufficient to mediate immediate transcriptional activation by TGF-. Transactivation of B sites by TGF- requires an intact NF-B pathway, cooperates with known activators of this pathway, and is mediated by Smad family members. Furthermore, we show that Smad3 interacts with 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.

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