Mitotic wnt signaling promotes protein stabilization and regulates cell size

Mol Cell. 2014 May 22;54(4):663-74. doi: 10.1016/j.molcel.2014.04.014. Epub 2014 May 15.


Canonical Wnt signaling is thought to regulate cell behavior mainly by inducing β-catenin-dependent transcription of target genes. In proliferating cells Wnt signaling peaks in the G2/M phase of the cell cycle, but the significance of this "mitotic Wnt signaling" is unclear. Here we introduce Wnt-dependent stabilization of proteins (Wnt/STOP), which is independent of β-catenin and peaks during mitosis. We show that Wnt/STOP plays a critical role in protecting proteins, including c-MYC, from GSK3-dependent polyubiquitination and degradation. Wnt/STOP signaling increases cellular protein levels and cell size. Wnt/STOP, rather than β-catenin signaling, is the dominant mode of Wnt signaling in several cancer cell lines, where it is required for cell growth. We propose that Wnt/STOP signaling slows down protein degradation as cells prepare to divide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Size*
  • Gene Expression Regulation
  • Glycogen Synthase Kinase 3 / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mitosis*
  • Protein Array Analysis
  • Protein Stability
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Ubiquitination
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway*


  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Wnt Proteins
  • Glycogen Synthase Kinase 3

Associated data

  • GEO/GSE50248
  • GEO/GSE50629