Regulation of Wnt/β-catenin signaling by herpesviruses

Figure 1 Canonical Wnt/β-catenin signaling pathway. In the absence of Wnt ligand stimulation, the β-catenin destruction complex - consisting of the proteins Axin, CK1, GSK-3α/β, APC, and DVL - phosphorylate β-catenin allowing β-TrCP to ubiquitinate β-catenin marking it for proteasomal degradation. When stimulated by Wnt ligands, engagement of the Fz receptor and co-receptors LRP5/6, induces signaling through DVL inhibiting the action of the destruction complex. This frees β-catenin from degradation pathways allowing β-catenin to translocate and accumulate in the nucleus. β-catenin mediated interaction with TCF family transcription factors and co-activators (CBP, etc.) and initiates transcription of target genes. APC: Adenomatous polyposis coli; β-TrCP: Beta-transducin repeat containing E3 ubiquitin protein ligase; CBP: CREB-binding protein; CK1: Casein kinase 1; DVL: Dishevelled; Fz: Frizzled receptor; GSK-3: Glycogen synthase kinase 3; LRP: Low-density lipoprotein receptor-related protein; TCF/LEF-1: T-cell factor/lymphoid enhancer-binding factor 1.