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Table 1 The location and function of components in Wnt signaling

From: The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy

Component Subcellular location Function
Wnt Secreted to extracellular matrix The ligands of the frizzled family, cause activation of TCF/LEF family transcription factors in the canonical Wnt signaling pathways
Dkk1 Extracellular region or secreted Inhibiting the interaction between LRP5/6 and Wnt
Dkk3 Extracellular region or secreted Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt, and promotes internalization of LRP5/6
LRP5/6 Plasma membrane, endoplasmic reticulum, membrane raft Co-receptor as a member of the frizzled family of seven-transmembrane spanning receptors
Frizzled Plasma membrane, endosome Receptor for Wnt proteins which are coupled to the beta-catenin canonical signaling pathway
RNF43 Plasma membrane, endoplasmic reticulum, nucleus A negative regulator of the Wnt signaling pathway by the ubiquitination, endocytosis, and degradation of Wnt receptor complex components Frizzled
ZNRF3 Plasma membrane A negative regulator of the Wnt signaling pathway by the ubiquitination and degradation of Wnt receptor complex components Frizzled and LRP6
Dvl Cytoplasm and cytosol, plasma membrane, cytoplasmic vesicle Binding to the frizzled family members and transducing the Wnt signal
Axin1 Plasma membrane, cytoplasm and cytosol, nucleus, membrane Component of the beta-catenin destruction complex that is required for down-regulating beta-catenin levels, modulates Wnt signal and controls dorsoventral patterning, enhances TGF-beta signaling and facilitates the phosphorylation of TP53
Axin2 Cytoplasm and cytosol Inhibitor of the Wnt signaling pathway by down-regulating beta-catenin
APC Plasma membrane, cytoskeleton, golgi apparatus, nucleus Component of the beta-catenin destruction complex, serves as a negative regulator of Wnt signaling and promotes degradation of beta-catenin, plays a role in hepatocyte growth factor-induced cell migration and the localization of MACF1 to cell membrane
GSK3 β Plasma membrane, cytoplasm and cytosol, nucleus An active protein kinase and component of the beta-catenin destruction complex, phosphorylates the N-terminus of beta-catenin and promotes its degradation
Tankyrase Cytoplasm and cytosol, cytoskeleton, golgi apparatus, nucleus, telomere An activator of Wnt signaling pathway by poly-ADP-ribosylation of Axin1 and Axin2, regulates telomere length and vesicle trafficking
β-TrCP Cytoplasm and cytosol, nucleus Component of the beta-catenin destruction complex and mediates the ubiquitination of beta-catenin
beta-catenin Plasma membrane, cytoplasm and cytosol, cytoskeleton, nucleus, adherens junction, cell junction, synapse beta-catenin accumulates in the nucleus as a coactivator of TCF/LEF family of transcription factors based on the occurrence of Wnt ligands, leading to the activation of Wnt response genes, it is involved in the regulation of cell adhesion, chondrocyte differentiation and centrosome cohesion
Groucho Nucleus Transcriptional corepressor
TCF1 Nucleus Transcriptional activator or repressor, beta-catenin binding, DNA binding
TCF3 Nucleus DNA-binding transcription factor activity, repressing transcription factor binding, bHLH transcription factor binding
CBP Cytoplasm and cytosol, nucleus beta-catenin-TCF complex assembly, acetylates histones and non-histone proteins, specifically binds to phosphorylated CREB and enhances its transcriptional activity, serves as a coactivator or transcriptional coactivator
Porcupine Endoplasmic reticulum palmitoleoyltransferase activity by modifying Wnt protein with the attachment of palmitoleate, a step required for efficient binding to frizzled receptors