Journal: Frontiers in cardiovascular medicine
Article Title: Pro-inflammatory role of Wnt/β-catenin signaling in endothelial dysfunction.
doi: 10.3389/fcvm.2022.1059124
Figure Lengend Snippet: FIGURE 1 Schematic diagrams of signal transduction in the canonical Wnt/β-catenin and canonical TNF-α-NFκB signaling pathways. (A) (Left panel) In the absence of a Wnt stimulus, β-catenin is phosphorylated by the destruction complex targeting it for poly-ubiquitination and subsequent proteasome-mediated proteolysis. Low cytoplasmic levels of β-catenin permit repression of LEF/TCF-dependent transcription by Groucho/TLE. (Right panel) Binding of Wnt ligands to the Frizzled/LRP5/6 receptor complex promotes recruitment of Disheveled and Axin, resulting in disassembly of the β-catenin destruction complex. Cytoplasmic accumulation of β-catenin allows for its nuclear translocation, where β-catenin displaces Groucho/TLE from LEF/TCF, enabling transcriptional regulation. (B) Binding of the TNF-α ligand to the TNF receptor recruits, phosphorylates and activates the IKK complex via oligomerisation of a series of adaptor proteins. In turn, the activated IKK complex phosphorylates IκBα, resulting in poly-ubiquitination of IκBα and its rapid proteasomal degradation. The unbound NFκB heterodimer complex, where p50 and p65 are members of NFκB family, translocates to the nucleus and regulates transcription of target genes involved inflammation. APC, adenomatous polyposis coli; GSK-3β, glycogen synthase kinase-3β; IκBα, inhibitor of κB-α; IKK, IκB kinase; LEF, lymphoid enhancer-building factor; LRP5/6, lipoprotein receptor-related protein 5/6; NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells; P, phosphorylation; TCF, T-cell factor; TLE, transducin-like enhancer of split; TNF-α, tumor necrosis factor-α; TNFR, tumor necrosis factor receptor.
Article Snippet: Primary antibodies included anti-ADAMTS13 IgG (Abcam; ab177940), anti-ICAM-1 IgG (Abcam; ab53013), anti-IκBα IgG (Cell Signaling Technology; 4814), anti-integrin αv IgG (Cell Signaling Technology; 4711), anti-integrin β3 IgG (Cell Signaling Technology; 13166), antiNFκB p65 IgG (Cell Signaling Technology; 8242), anti-VCAM-1 IgG (Abcam; ab134047), and anti-von Willebrand factor IgG (Cell Signaling; 65707S).
Techniques: Transduction, Protein-Protein interactions, Ubiquitin Proteomics, Binding Assay, Translocation Assay, Phospho-proteomics