β-Catenin and The β-Catenin Destruction Complex: From Basic Science to Drug Design
- VernacularTitle:β-Catenin and The β-Catenin Destruction Complex: From Basic Science to Drug Design
- Author:
Xu WENQING
;
Kimelman DAVID
- Publication Type:Journal Article
- Keywords:
Wnt pathway;
β-catenin;
β-catenin destruction complex;
APC;
cancer;
stem cell;
intercellular signaling
- From:
Progress in Biochemistry and Biophysics
2005;32(10):903-911
- CountryChina
- Language:Chinese
-
Abstract:
The canonical Wnt/β-catenin signaling pathway plays critical roles in both embryonic development and tumorigenesis. Central to the pathway is the turnover of β-catenin, a protein that functions in both cell adhesion and transcription. In the absence of a Wnt signal, free cytosolic β-catenin is phosphorylated by a large protein complex called the "β-catenin destruction complex" that targets β-catenin for degradation by an ubiquitin ligase/proteasome system. In the presence of a Wnt signal, the binding of Wnt to its receptor Frizzled and co-receptor LRP leads to the inhibition of β-catenin phosphorylation in the β-catenin destruction complex through an unknown mechanism. Inhibition of the β-catenin destruction complex leads to the accumulation of nuclear β-catenin, which in turn forms a complex with Tcf and BCL9. Recent studies have provided important clues regarding the molecular mechanism of the β-catenin destruction complex as well as an explanation for how β-catenin switches between its roles in cell adhesion and transcription.
