Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

SMIF, a Smad4-interacting protein that functions as a co- activator in TGFβ signalling


Hammerschmidt,  Matthias
Georges Köhler Laboratory, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

Bai, R.-Y., Koester, C., Ouyang, T., Hahn, S. A., Hammerschmidt, M., Peschel, C., et al. (2002). SMIF, a Smad4-interacting protein that functions as a co- activator in TGFβ signalling. Nature Cell Biology, 4(3), 181-190.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-965D-5
Proteins of the transforming growth factor β (TGFβ) superfamily regulate diverse cellular responses, including cell growth and differentiation. After TGFβ stimulation, receptor-associated Smads are phosphorylated and form a complex with the common mediator Smad4. Here, we report the cloning of SMIF, a ubiquitously expressed, Smad4-interacting transcriptional co-activator. SMIF forms a TGFβ/bone morphogenetic protein 4 (BMP4)-inducible complex with Smad4, but not with others Smads, and translocates to the nucleus in a TGFβ/BMP4-inducible and Smad4-dependent manner. SMIF possesses strong intrinsic TGFβ-inducible transcriptional activity, which is dependent on Smad4 in mammalian cells and requires p300/CBP. A point mutation in Smad4 abolished binding to SMIF and impaired its activity in transcriptional assays. Overexpression of wild-type SMIF enhanced expression of TGFβ/BMP regulated genes, whereas a dominant-negative SMIF mutant suppressed expression. Furthermore, dominant-negative SMIF is able to block TGFβ-induced growth inhibition. In a knockdown approach with morpholinoantisense oligonucleotides targeting zebrafish SMIF, severe but distinct phenotypic defects were observed in zebrafish embryos. Thus, we propose that SMIF is a crucial activator of TGFβ signalling.