Wnt/beta-catenin signaling induces the expression and activity of betaTrCP ubiquitin ligase receptor.
Beta-transducing repeat-containing protein (betaTrCP) targets the ubiquitination and subsequent degradation of both beta-catenin and IkappaB, thereby playing an important role in beta-catenin/Tcf and NF-kappaB-dependent signaling. Here evidence is presented that beta-catenin/Tcf signaling elevates the expression of betaTrCP mRNA and protein in a Tcf-dependent manner, which does not require betaTrCP transcription. Induction of betaTrCP expression by the beta-catenin/Tcf pathway results in an accelerated degradation of the wild-type beta-catenin, suggesting that the negative feedback loop regulation may control the beta-catenin/Tcf pathway. This signaling also upregulated NF-kappaB transactivation without affecting the activity of IkappaB kinase, thereby establishing that the maintenance of the betaTrCP level is important for coordination between beta-catenin/Tcf and NF-kappaB signaling.
Spiegelman
V S
VS
AMC Cancer Research Center, Denver, Colorado 80214, USA.
Slaga
T J
TJ
Pagano
M
M
Minamoto
T
T
Ronai
Z
Z
Fuchs
S Y
SY
D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006367:HeLa Cells; D006801:Humans; D007413:Intestinal Mucosa; D007420:Intestine, Large; D008025:Ligases / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*; D015854:Up-Regulation; D051154:Wnt2 Protein; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins
C471644:BTRC protein, human; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D014452:Ubiquitins; D051154:Wnt2 Protein; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; D044767:Ubiquitin-Protein Ligases; D019204:GTP-Binding Proteins; D008025:Ligases