ISSN:
1420-9071
Keywords:
Key words.β-Catenin; lymphoid enhancer factor/T cell factor (Lef/Tcf); wnt; dishevelled (dsh); glycogen synthase kinase 3 (GSK3); adenomatous polyposis coli (APC); integrin-linked kinase (ILK); cadherin.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract. β-Catenin plays a structural role in cell adhesion by binding to cadherins at the intracellular surface of the plasma membrane and a signaling role in the cytoplasm as the penultimate downstream mediator of the wnt signaling pathway. The ultimate mediator of this pathway is a nuclear complex of β-catenin acting as a coactivtor with lymphoid enhancer factor/T cell factor (Lef/Tcf) transcription factors to stimulate transcription of a variety of target genes. Signaling through β-catenin is regulated by modulating its degradation and nuclear translocation. In the absence of an activating signal, phosphorylation of β-catenin by glycogen synthase kinase 3 (GSK3) acting in conjunction with adenomatous polyposis coli and axin/conductin causes β-catenin to interact with the β-transducin repeat-containing protein which results in its ubiquitination and degradation. Signaling from the wnt pathway activates dishevelled which, in an as yet undefined manner, inhibits the activity of GSK3 resulting in an increase in the cytoplasmic free pool of β-catenin, and translocation into the nucleus. The integrin-linked kinase (ILK) pathway also activates β-catenin-Lef/Tcf signaling. ILK phosphorylates GSK3 to inhibit its activity and translocates β-catenin into the nucleus. In addition, ILK downregulates the expression of E-cadherin and upregulates Lef-1 expression. In the final step of the β-catenin-Lef/Tcf signaling pathway, nuclear β-catenin binds pontin52-TATA binding protein and displaces Groucho-related gene or CREB-binding protein corepressors from Lef/Tcf resulting in stimulation of transcription. During development, β-catenin-Lef/Tcf signaling is involved in the formation of dorsal mesoderm and dorsal axis. Furthermore, defects in the β-catenin-Lef/Tcf pathway are involved in the development of several types of cancers.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s000180050449
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