Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation

Mol Cell Biochem. 2005 Mar;271(1-2):23-8. doi: 10.1007/s11010-005-3456-7.


Tsc-22 was isolated as a TGF-beta-inducible gene by differential screening of the mouse osteoblastic cell cDNA library [J Biol Chem 267 (1992) 10219]. tsc-22 mRNA is expressed in almost all organs of mice and humans and its expression is induced in a variety of cell lines by many different factors including TGF-beta, phorbol ester, serum, and progestin. tsc-22 encodes a 18-kd protein that contains a leucine zipper motif and a Tsc-box. The leucine zipper motif of the Tsc-22 protein does not have a basic DNA binding motif and when the protein was fused to a heterologous DNA binding domain, it showed various transcription-modulating activities ranging from activation to repression [J Biol Chem 274 (1999) 27439, Biochem Biophys Res Commun 278 (2000) 659]. Although these results suggest that the Tsc-22 protein functions as a transcriptional regulator recruiting various coactivators or repressors, its mechanism is not known. In this study, we examined whether Tsc-22 modulates the TGF-beta-dependant signaling pathway and found that Tsc-22 binds to and modulate the transcriptional activity of Smad3 and Smad4. Its effect on cellular differentiation was also examined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythroid Cells / cytology*
  • Erythroid Cells / metabolism
  • Humans
  • K562 Cells
  • Mutation
  • Protein Interaction Mapping
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription, Genetic
  • Transforming Growth Factor beta / metabolism*


  • DNA-Binding Proteins
  • Repressor Proteins
  • SMAD3 protein, human
  • SMAD4 protein, human
  • Smad3 Protein
  • Smad4 Protein
  • TSC22D1 protein, human
  • Trans-Activators
  • Transforming Growth Factor beta