Coiled-coil domain containing 85B suppresses the beta-catenin activity in a p53-dependent manner.
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.
Iwai
A
A
Division of Gastroenterology and Hepatology, Department of Medicine, Kyoto University, Kyoto, Japan.
Hijikata
M
M
Hishiki
T
T
Isono
O
O
Chiba
T
T
Shimotohno
K
K
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007976:Leupeptins / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C101409:CCDC85B protein, human; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D007976:Leupeptins; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C495901:TP53 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde