Regulation of Wnt signaling by protein-protein interaction and post-translational modifications.
The Wnt signaling pathway is conserved in various species from worms to mammals, and plays important roles in cellular proliferation, differentiation, and migration. Wnt stabilizes cytoplasmic beta-catenin and then the accumulated beta-catenin is translocated into the nucleus, where it activates the transcriptional factor T-cell factor (Tcf)/lymphoid enhancer factor (Lef), and thereby stimulates the expression of genes including c-myc, c-jun, fra-1, and cyclin D1. Tight regulation of this response involves post-translational modifications of the components of the Wnt signaling pathway. Phosphorylation, ubiquitination, and sumoylation have been shown to affect the half-life of beta-catenin and the transcriptional activity of Tcf/Lef. The precise spatio-temporal patterns of these multiple modifications determine the driving force of various cellular responses.
Kikuchi
Akira
A
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. akikuchi@hiroshima-u.ac.jp
Kishida
Shosei
S
Yamamoto
Hideki
H
D000818:Animals; D001665:Binding Sites; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D051153:Wnt Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
D051820:TCF Transcription Factors; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin