Table 1 The main components of the Wnt/β-catenin signaling pathway
From: Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy
Components | Full name | Role in Wnt/β-catenin signaling pathway |
|---|---|---|
Wnt | Wingless and INT1 | Main ligands that activate the Wnt/β-catenin signaling pathway |
PORCN | Porcupine | A membrane bound O-acyltransferases that adds palmitoleate groups to Wnt proteins |
WLS | Wntless | Binding to lipid-modified Wnts and contribute to Wnt secretory |
FZD | Frizzled | Wnt ligands bind to Wnt proteins and activate the Wnt/β-catenin signaling pathway |
LRP5/6 | Lipoprotein receptor-related proteins 5 and 6 | Form cell surface receptor complexes with FZD |
DVL | Dishevelled | Protein recruited to the FZD–LRP5 and FZD–LRP6 complex in the presence of Wnt ligands and enabling the transduction of Wnt signalling |
APC | Adenomatous polyposis coli | Forming the β-catenin destruction complex with CK1, AXIN, GSK3β |
AXIN | Axin | Forming the β-catenin destruction complex with CK1, APC, GSK3β |
CK1α | Casein kinase 1α | Forming the β-catenin destruction complex and phosphorylating the β-catenin at Ser45 |
GSK3β | Glycogen synthase kinase 3β | Forming the β-catenin destruction complex and phosphorylating the β-catenin at Thr41, Ser33, Ser37 |
β-catenin | β-catenin | A central molecule in the Wnt/β-catenin signaling pathway that translocates from the cytoplasm to the nucleus and mediates TCF–LEF-dependent gene expression |
TCF/LEF | T cell factor–lymphoid enhancer factor | Transcriptional factors that bound to β-catenin in the nucleus and activate target gene transcription. |
β-TrCP | β-transducin repeat-containing protein | Binding to phosphorylated β-catenin and leading to its degradation |
WIF | Wnt inhibitory factor | Binding with Wnt proteins and preventing its interaction with the receptor complex |
sFRP | Soluble frizzled-related protein | Extracellular inhibitors of Wnt signaling by binding to Wnt ligands and preventing their interaction with Frizzled receptors |
GPCs | Glypicans | Co-receptors for Wnt ligands by interacting with both the Wnt ligands and the Frizzled receptors |
Tiki | Tiki | A membrane bound proteases that cleave and inactivate Wnt proteins |
Notum | Notum | Inhibiting the activation and secretion of Wnt ligands by removing the lipid modification of palmitoleate in Wnt proteins |
R-spondin | Roof plate-specific spondins | The ligands for LGR4/5 and upregulation of Wnt signalling |
Norrin | Norrin | A ligand interacts with FZD4 and LRP5/6 leading to the activation of downstream signaling |
RNF43 | Ring Finger Protein 43 | A negative regulator of the Wnt pathway by promoting the degradation of the Frizzled/LRP5/6 complex |
DKKs | Dickkopf | Antagonists of the Wnt signaling pathway by inhibiting the formation of the Wnt-Frizzled-LRP5/6 complex. |
Dab2 | Disabled-2 | Negative regulator of the Wnt signaling by facilitating the degradation of the Wnt receptor complex and interacting with DVL and AXIN |
FOXK1/ FOXK2 | Forkhead box protein K1/K2 | Transcriptional co-repressors of Wnt target genes and DVL-interacting proteins by translocating DVL into the nucleus |
PP2A | Protein phosphatase 2 A | A protein phosphatase that dephosphorylates β-catenin |