Inactivating mutations of the adenomatous polyposis coli gene (APC) or activating mutations of the -catenin gene (CTNNB1) initiate colorectal neoplasia. To address the biochemical and physiologic effects of mutant -catenin, we disrupted either the mutant or wild-type CTNNB1 allele in a human colorectal cancer cell line. Cells with only wild-type -catenin had decreased colony-forming ability whe...

Several recent studies have shown that proteins of the cadherin-catenin complex are not only involved in cell-cell adhesion but also in the proliferation and differentiation processes. For the first time, we investigated the effect of the quantity of cytoplasmic beta-catenin on dermal fibroblast proliferation by overexpressing human beta-catenin in human dermal fibroblasts. Our results show tha...

Beta-catenin signaling has recently been tied to the emergence of tolerogenic dendritic cells (DCs). In this article, we demonstrate a novel role for beta-catenin in directing DC subset development through IFN regulatory factor 8 (IRF8) activation. We found that splenic DC precursors express beta-catenin, and DCs from mice with CD11c-specific constitutive beta-catenin activation upregulated IRF...

Accumulated evidence suggests that aberrant regulation of δ-catenin leads to pathological consequences such as mental retardation and cognitive dysfunction. This study revealed that 14-3-3ɛ/ζ stabilizes δ-catenin, with different binding regions involved in the interaction. Furthermore, the specific inhibition of the interaction of 14-3-3 with δ-catenin reduced levels of δ-catenin and significan...

The cadherin/catenin complex plays important roles in cell adhesion, signal transduction, as well as the initiation and maintenance of structural and functional organization of cells and tissues. In the preceding study, we showed that the assembly of the cadherin/catenin complex is temporally regulated, and that novel combinations of catenin and cadherin complexes are formed in both Triton X-10...

The stability and subcellular localization of beta-catenin, a protein that plays a major role in cell adhesion and proliferation, is tightly regulated by multiple signaling pathways. While aberrant activation of beta-catenin signaling has been implicated in cancers, the biochemical identity of transcriptionally active beta-catenin (ABC), commonly known as unphosphorylated serine 37 (S37) and th...

Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. While the pathogenesis of silicosis is not clearly understood, the Wnt/β-catenin signaling pathway is thought to play a major role in lung fibrosis. To explore the role of Wnt/β-catenin pathway in silicosis, we blocked Wnt/β-catenin pathway both in silica-treated MLE-12 cells (a mouse pulmonary epi...

Chondrogenesis is a multistep process that is essential for endochondral bone formation. Previous results have indicated a role for -catenin and Wnt signaling in this pathway. Here we show the existence of physical and functional interactions between -catenin and Sox9, a transcription factor that is required in successive steps of chondrogenesis. In vivo, either overexpression of Sox9 or inacti...

β-Catenin is a multifunctional protein with critical roles in cell-cell adhesion, Wnt signaling, and the centrosome cycle. Whereas the regulation of β-catenin in cell-cell adhesion and Wnt signaling are well understood, how β-catenin is regulated at the centrosome is not. NIMA-related protein kinase 2 (Nek2), which regulates centrosome disjunction/splitting, binds to and phosphorylates β-cateni...

Synaptic scaffolding molecule (S-SCAM) is a synaptic membrane-associated guanylate kinase with inverted domain organization (MAGI) that interacts with NMDA receptor subunits and neuroligin. In epithelial cells, the non-neuronal isoform of S-SCAM (MAGI-1) is localized at tight or adherens junctions. Recent studies have revealed that the polarized targeting of MAGI-1 to the lateral membrane is me...