Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cytoskeletal Proteins / metabolism*
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GTP-Binding Proteins / biosynthesis*
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HeLa Cells
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Humans
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Intestinal Mucosa
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Intestine, Large
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Ligases / metabolism*
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NF-kappa B / genetics
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / metabolism
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Transcriptional Activation
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Ubiquitin-Protein Ligases
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Ubiquitins / metabolism*
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Up-Regulation
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Wnt2 Protein
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beta Catenin
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beta-Transducin Repeat-Containing Proteins
Substances
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BTRC protein, human
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CTNNB1 protein, human
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Cytoskeletal Proteins
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NF-kappa B
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Proto-Oncogene Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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Ubiquitins
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Wnt2 Protein
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beta Catenin
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beta-Transducin Repeat-Containing Proteins
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Ubiquitin-Protein Ligases
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GTP-Binding Proteins
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Ligases