Cover Image

imageOn the Cover: Model of Wnt/β‐catenin pathway in the presence and absence of Wnt ligand. This model illustrates the Wnt/β‐catenin pathway's activity in response to the presence or absence of the Wnt ligand. Without Wnt, the proteins APC, Axin, CK1, DVL, and GSK3 constitute the destruction complex that controls β‐catenin levels, influencing Wnt signaling. Upon Wnt ligand binds with the Frizzled (Fz) receptor and the LRP6 co‐receptor, GSK3 translocates to the membrane and is then internalized into an early endosome and subsequently into multivesicular bodies (MVBs). This process, which sequesters GSK3 and the destruction complex, triggers macropinocytosis in the Wnt pathway. In the cell nucleus, β‐catenin forms an active complex with LEF (lymphoid enhancer factor) and TCF (T‐cell factor) proteins by displacing TLE/Groucho complexes and recruitment of histone‐modifying co‐activators such as CBP/p300, BRG1, BCL9, and Pygo. Such a transcriptional switch leads to a change in multiple cellular processes, such as the activation of genes involved in proliferation and cell migration. Additionally, the transmembrane E3 ligases RNF43/ZNRF3 represent important elements down regulators of the Wnt signaling through the ubiquitination and degradation of the Fzd/Lrp5/6 receptor complex via the endolysosomal pathway. While β‐catenin is recognized as an important oncogene, it is also pivotal for cell adhesion as a structural component of the cadherin complex structure (detailed in Fig. 3). (Figure created with BioRender.com, accessed on 11 July 2023).