Abstract
Aberrant accumulation of beta-catenin is closely related to carcinogenesis. Mutations in the p53 gene are reported to induce the aberrant accumulation of beta-catenin in the absence of dysfunction in the glycogen synthase kinase 3beta (GSK3beta)-mediated degradation pathway, but the mechanism remains incompletely understood. Here, we show that human coiled-coil domain containing 85B (CCDC85B) is induced by p53 and regulates beta-catenin activity via interaction with the T-cell factor 4 in the nucleus. Moreover, CCDC85B enhances the degradation of beta-catenin and suppresses tumor cell growth. In conclusion, we revealed that CCDC85B-induced degradation of beta-catenin is independent of GSK3beta and other p53-inducible products, Siah-1L, suggesting that CCDC85B constitutes the one of the frameworks of p53-induced multiple regulatory pathways for beta-catenin activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Carrier Proteins / physiology*
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Cell Nucleus / metabolism
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Cells, Cultured
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Cysteine Proteinase Inhibitors / pharmacology
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Fluorescent Antibody Technique
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Gene Expression Profiling
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Hepatocyte Nuclear Factor 1-alpha / antagonists & inhibitors
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Hepatocyte Nuclear Factor 1-alpha / genetics
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Hepatocyte Nuclear Factor 1-alpha / metabolism
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Humans
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Immunoblotting
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Immunoprecipitation
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Leupeptins / pharmacology
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Oligonucleotide Array Sequence Analysis
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Repressor Proteins
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Reverse Transcriptase Polymerase Chain Reaction
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TCF Transcription Factors / genetics
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TCF Transcription Factors / metabolism
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Transcription Factor 7-Like 2 Protein
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Transfection
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Tumor Suppressor Protein p53 / metabolism*
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Ubiquitin / metabolism
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beta Catenin / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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CCDC85B protein, human
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Carrier Proteins
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Cysteine Proteinase Inhibitors
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HNF1A protein, human
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Hepatocyte Nuclear Factor 1-alpha
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Leupeptins
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Repressor Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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TP53 protein, human
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Transcription Factor 7-Like 2 Protein
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Tumor Suppressor Protein p53
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Ubiquitin
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beta Catenin
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Glycogen Synthase Kinase 3
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde