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 phosphorylationindependent 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.
|Number of pages||6|
|Journal||Molecules and cells|
|Publication status||Published - 2016 Nov 1|
Bibliographical noteFunding Information:
This work was supported by grants from the National R&D program for Cancer Control, Ministry of Health & Welfare (0720540), the National Research Foundation of Korea (NRF) funded by the Korea government (MESF; 2014R1A2A1A11053203), Seoul National University Hospital (SNUH) Research Fund, Republic of Korea (3420130270 and 0320140100), This work was supported by the Brain Korea 21 PLUS program.
© The Korean Society for Molecular and Cellular Biology. All rights reserved.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology