Smads bind directly to the Jun family of AP-1 transcription factors.

Published

Journal Article

Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGFbeta) and activate transcription. Recent evidence implicates Smad3 and Smad4 in the transcriptional activation of consensus AP-1 DNA-binding sites that do not interact with Smads directly. Here, we report that Smad3 and Smad4 can physically interact with AP-1 family members. In vitro binding studies demonstrate that both Smad3 and Smad4 bind all three Jun family members: JunB, cJun, and JunD. The Smad interacting region of JunB maps to a C-terminal 20-amino acid sequence that is partially conserved in cJun and JunD. We show that Smad3 and Smad4 also associate with an endogenous form of cJun that is rapidly phosphorylated in response to TGFbeta. Providing evidence for the importance of this interaction between Smad and Jun proteins, we demonstrate that Smad3 is required for the activation of concatamerized AP-1 sites in a reporter construct that has previously been characterized as unable to bind Smad proteins directly. Together, these data suggest that TGFbeta-mediated transcriptional activation through AP-1 sites may involve a regulated interaction between Smads and AP-1 transcription factors.

Full Text

Duke Authors

Cited Authors

  • Liberati, NT; Datto, MB; Frederick, JP; Shen, X; Wong, C; Rougier-Chapman, EM; Wang, XF

Published Date

  • April 27, 1999

Published In

Volume / Issue

  • 96 / 9

Start / End Page

  • 4844 - 4849

PubMed ID

  • 10220381

Pubmed Central ID

  • 10220381

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.9.4844

Language

  • eng

Conference Location

  • United States