What is beta-catenin destruction complex?
The beta-catenin destruction complex plays a key role in the canonical Wnt signaling pathway. In the absence of Wnt signaling, this complex controls the levels of cytoplamic beta-catenin. Beta-catenin associates with and is phosphorylated by the destruction complex.
Which protein are components of the beta-catenin destruction complex?
The β‐catenin destruction complex is a dynamic cytosolic multiprotein assembly that provides a key node in Wnt signalling regulation. The core components of the destruction complex comprise the scaffold proteins axin and adenomatous polyposis coli and the Ser/Thr kinases casein kinase 1 and glycogen synthase kinase 3.
What is the destruction complex?
The destruction complex is likely a dynamic multiprotein assembly, but its core components include, in addition to β-catenin itself, the Ser/Thr kinases glycogen synthase kinase 3 (GSK-3) and casein kinase 1 (CK1), the scaffolding protein Axin, the adenomatous polyposis coli (APC) protein, and the E3-ubiquitin ligase β …
How does APC regulate beta-catenin?
The adenomatous polyposis coli (APC) tumor suppressor protein plays a critical role in regulating cellular levels of the oncogene product β-catenin. APC binds to β-catenin through a series of homologous 15 and 20 amino acid repeats.
What happens when beta-catenin is phosphorylated?
β-Catenin is phosphorylated on its N-terminus by GSK3 (shown in orange) and CKI (shown in orange). These phosphorylations target β-catenin for ubiquitination and subsequent proteasomal degradation.
What is Wnt β-catenin pathway?
The canonical Wnt pathway (or Wnt/β-catenin pathway) is the Wnt pathway that causes an accumulation of β-catenin in the cytoplasm and its eventual translocation into the nucleus to act as a transcriptional coactivator of transcription factors that belong to the TCF/LEF family.
What Signalling pathway is APC involved?
Wnt/β-catenin signaling pathway
Adenomatous polyposis coli (APC) protein has been thought to function as a tumor suppressor through its involvement in the Wnt/β-catenin signaling pathway.
What does APC mutation do?
In 1997, a Johns Hopkins research team found an inherited genetic mutation called APC I1307K. Adenomatous polyposis coli (APC) is a gene that suppresses tumor growth. If the APC gene is defective, it makes the gene unstable and more susceptible to additional changes that may lead to colon and rectal cancers.
Is phosphorylation used in Wnt pathway?
Phosphorylation represents a key mechanism responsible for the tight control of β-catenin levels within normal cells and the activation of the Wnt/β-catenin pathway (Figure 2).
What is beta-catenin mutation?
The CTNNB1 gene mutations that cause desmoid tumors usually occur in a region of the gene called exon 3. They change single protein building blocks (amino acids) in the beta-catenin protein. These mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed.
What is beta catenin signaling?
Wnt/β-catenin signaling, a highly conserved pathway through evolution, regulates key cellular functions including proliferation, differentiation, migration, genetic stability, apoptosis, and stem cell renewal.
What is the function of the β catenin destruction complex?
At the heart of the canonical Wnt signaling pathway is the β -catenin destruction complex, which functions in the absence of Wnt signaling to keep the cytosolic and nuclear levels of β -catenin very low by promoting the phosphorylation and ubiquitination of β -catenin.
What is the structure of the β-catenin destruction complex?
The destruction complex is likely a dynamic multiprotein assembly, but its core components include, in addition to β-catenin itself, the Ser/Thr kinases glycogen synthase kinase 3 (GSK-3) and casein kinase 1 (CK1), the scaffolding protein Axin, the adenomatous polyposis coli (APC) protein, and the E3-ubiquitin ligase β-TrCP ( Fig. 1 ).
What happens to β-catenin in the absence of Wnt?
In the absence of a Wnt stimulus, the transcriptional coactivator β-catenin is degraded by a multiprotein “destruction complex” that includes the tumor suppressors Axin and adenomatous polyposis coli (APC), the Ser/Thr kinases GSK-3 and CK1, protein phosphatase 2A (PP2A), and the E3-ubiquitin ligase β-TrCP.
What is the role of protein phosphatase 1 in catenin degradation?
Curr. Biol. 15, 1989–1997 (2005). 35. Luo, W. et al. Protein phosphatase 1 regulates assembly and function of the β-catenin degradation complex. EMBO J. 26, 1511–1521 (2007). 36. Roberts, D. M. et al. Deconstructing the ßcatenin destruction complex: mechanistic roles for the tumor suppressor APC in regulating Wnt signaling. Mol.