The functions and regulation of Smurfs in cancers

Semin Cancer Biol. 2020 Dec;67(Pt 2):102-116. doi: 10.1016/j.semcancer.2019.12.023. Epub 2019 Dec 30.


Smad ubiquitination regulatory factor 1 (Smurf1) and Smurf2 are HECT-type E3 ubiquitin ligases, and both Smurfs were initially identified to regulate Smad protein stability in the TGF-β/BMP signaling pathway. In recent years, Smurfs have exhibited E3 ligase-dependent and -independent activities in various kinds of cells. Smurfs act as either potent tumor promoters or tumor suppressors in different tumors by regulating biological processes, including metastasis, apoptosis, cell cycle, senescence and genomic stability. The regulation of Smurfs activity and expression has therefore emerged as a hot spot in tumor biology research. Further, the Smurf1- or Smurf2-deficient mice provide more in vivo clues for the functional study of Smurfs in tumorigenesis and development. In this review, we summarize these milestone findings and, in turn, reveal new avenues for the prevention and treatment of cancer by regulating Smurfs.

Keywords: Cancer; E3 ligase; Smurf1; Smurf2; Ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genes, Tumor Suppressor
  • Humans
  • Mice, Knockout
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*


  • SMURF1 protein, human
  • SMURF2 protein, human
  • Smurf1 protein, mouse
  • Smurf2 protein, mouse
  • Ubiquitin-Protein Ligases