STAT3 Potentiates SIAH-1 Mediated Proteasomal Degradation of β-Catenin in Human Embryonic Kidney Cells

Mol Cells. 2016 Nov 30;39(11):821-826. doi: 10.14348/molcells.2016.0212. Epub 2016 Nov 18.


The β-catenin functions as an adhesion molecule and a component of the Wnt signaling pathway. In the absence of the Wnt ligand, β-catenin is constantly phosphorylated, which designates it for degradation by the APC complex. This process is one of the key regulatory mechanisms of β-catenin. The level of β-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a phosphorylation-independent degradation pathway. Similar to β-catenin, STAT3 is responsible for various cellular processes, such as survival, proliferation, and differentiation. However, little is known about how these molecules work together to regulate diverse cellular processes. In this study, we investigated the regulatory relationship between STAT3 and β-catenin in HEK293T cells. To our knowledge, this is the first study to report that β-catenin-TCF-4 transcriptional activity was suppressed by phosphorylated STAT3; furthermore, STAT3 inactivation abolished this effect and elevated activated β-catenin levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active β-catenin via degradation, which stabilized SIAH-1 and increased its interaction with β-catenin. These results suggest that activated STAT3 regulates active β-catenin protein levels via stabilization of SIAH-1 and the subsequent ubiquitin-dependent proteasomal degradation of β-catenin in HEK293T cells.

Keywords: SIAH-1; STAT3; proteasomal degradation; β-catenin.

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • HEK293 Cells
  • Humans
  • Kidney / cytology
  • Kidney / embryology
  • Kidney / metabolism
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Transcription Factor 4
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection
  • Ubiquitin-Protein Ligases / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CTNNB1 protein, human
  • Nuclear Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors
  • beta Catenin
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • Proteasome Endopeptidase Complex