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Crosstalk between nuclear factor I-C and transforming growth factor-β1 signaling regulates odontoblast differentiation and homeostasis.

Transforming growth factor-β1 (TGF-β1) signaling plays a key role in vertebrate development, homeostasis, and disease. Nuclear factor I-C (NFI-C) has been implicated in TGF-β1 signaling, extracellular matrix gene transcription, and tooth root development. However, the functional relationship between NFI-C and TGF-β1 signaling remains uncharacterized. The purpose of this study was to identify the molecular interactions between NFI-C and TGF-β1 signaling in mouse odontoblasts. Real-time polymerase chain reaction and western analysis demonstrated that NFI-C expression levels were inversely proportional to levels of TGF-β1 signaling molecules during in vitro odontoblast differentiation. Western blot and immunofluorescence results showed that NFI-C was significantly degraded after TGF-β1 addition in odontoblasts, and the formation of the Smad3 complex was essential for NFI-C degradation. Additionally, ubiquitination assay results showed that Smurf1 and Smurf2 induced NFI-C degradation and polyubiquitination in a TGF-β1-dependent manner. Both kinase and in vitro binding assays revealed that the interaction between NFI-C and Smurf1/Smurf2 requires the activation of the mitogen-activated protein kinase pathway by TGF-β1. Moreover, degradation of NFI-C induced by TGF-β1 occurred generally in cell types other than odontoblasts in normal human breast epithelial cells. In contrast, NFI-C induced dephosphorylation of p-Smad2/3. These results show that crosstalk between NFI-C and TGF-β1 signaling regulates cell differentiation and homeostatic processes in odontoblasts, which might constitute a common cellular mechanism.

Pubmed ID: 22195013


  • Lee DS
  • Yoon WJ
  • Cho ES
  • Kim HJ
  • Gronostajski RM
  • Cho MI
  • Park JC


PloS one

Publication Data

December 23, 2011

Associated Grants


Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Line
  • Enzyme Activation
  • Gene Expression Regulation
  • HEK293 Cells
  • Homeostasis
  • Humans
  • MAP Kinase Signaling System
  • Mice
  • Models, Biological
  • NFI Transcription Factors
  • Odontoblasts
  • Phosphorylation
  • Protein Binding
  • Proteolysis
  • Signal Transduction
  • Smad2 Protein
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Ubiquitin-Protein Ligases
  • Ubiquitination