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Gene Review

Smurf1  -  SMAD specific E3 ubiquitin protein ligase 1

Mus musculus

Synonyms: 4930431E10Rik, E3 ubiquitin-protein ligase SMURF1, SMAD ubiquitination regulatory factor 1, SMAD-specific E3 ubiquitin-protein ligase 1, mKIAA1625
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Disease relevance of Smurf1


High impact information on Smurf1


Biological context of Smurf1


Anatomical context of Smurf1

  • Smurf1 therefore appears to be an important regulatory factor in osteoblast differentiation and a potential molecular target for identification of bone anabolic agents [4].
  • Overexpression of Smurf1 in airway epithelial cells by intratracheal introduction of recombinant adenoviral vector dramatically inhibited embryonic day (E) 11.5 lung explant growth in vitro [5].
  • We treated C2C12 and 2T3 osteoblast precursor cell lines and primary osteoblasts with TNF and found that TNF, but not interleukin-1, significantly increased Smurf1 and Smurf2 expression [2].

Physical interactions of Smurf1


Regulatory relationships of Smurf1

  • Smurf1 has been found to interact with BMP-activated Smad1 and -5 and to mediate degradation of these Smad proteins [3].

Other interactions of Smurf1

  • Recently we have found that Smurf1 mediates the protein degradation of the osteoblast-specific transcription factor Runx2/Cbfa1 [3].
  • Studies at the cellular level show that overexpression of Smurf1 reduced epithelial cell proliferation and differentiation, as documented by reduced PCNA-positive cell index and by reduced mRNA levels for surfactant protein C and Clara cell protein 10 expression [5].
  • TNF inhibited the expression of bone morphogenetic protein and transforming growth factor-beta signaling reporter constructs, and the inhibition of each was blocked by Smurf1 siRNA and Smurf2 siRNA, respectively [2].

Analytical, diagnostic and therapeutic context of Smurf1


  1. Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia. Horiki, M., Imamura, T., Okamoto, M., Hayashi, M., Murai, J., Myoui, A., Ochi, T., Miyazono, K., Yoshikawa, H., Tsumaki, N. J. Cell Biol. (2004) [Pubmed]
  2. Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. Kaneki, H., Guo, R., Chen, D., Yao, Z., Schwarz, E.M., Zhang, Y.E., Boyce, B.F., Xing, L. J. Biol. Chem. (2006) [Pubmed]
  3. Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo. Zhao, M., Qiao, M., Harris, S.E., Oyajobi, B.O., Mundy, G.R., Chen, D. J. Biol. Chem. (2004) [Pubmed]
  4. E3 ubiquitin ligase Smurf1 mediates core-binding factor alpha1/Runx2 degradation and plays a specific role in osteoblast differentiation. Zhao, M., Qiao, M., Oyajobi, B.O., Mundy, G.R., Chen, D. J. Biol. Chem. (2003) [Pubmed]
  5. Overexpression of Smurf1 negatively regulates mouse embryonic lung branching morphogenesis by specifically reducing Smad1 and Smad5 proteins. Shi, W., Chen, H., Sun, J., Chen, C., Zhao, J., Wang, Y.L., Anderson, K.D., Warburton, D. Am. J. Physiol. Lung Cell Mol. Physiol. (2004) [Pubmed]
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