Cullin4B/E3-ubiquitin ligase negatively regulates beta-catenin.
Beta-catenin is the key transducer of Wingless-type MMTV integration site family member (Wnt) signalling, upregulation of which is the cause of cancer of the colon and other tissues. In the absence of Wnt signals, beta-catenin is targeted to ubiquitin-proteasome-mediated degradation. Here we present the functional characterization of E3-ubiquitin ligase encoded by cul4B. RNAi-mediated knock-down of Cul4B in a mouse cell line C3H T10 (1/2) results in an increase in beta-catenin levels. Loss-of-function mutation in Drosophila cul4 also shows increased beta-catenin/Armadillo levels in developing embryos and displays a characteristic naked-cuticle phenotype. Immunoprecipitation experiments suggest that Cul4B and beta-catenin are part of a signal complex in Drosophila, mouse and human. These preliminary results suggest a conserved role for Cul4B in the regulation of beta-catenin levels.
Tripathi
Rachana
R
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
Kota
Satya Keerthi
SK
Srinivas
Usha K
UK
D000818:Animals; D030801:Animals, Genetically Modified; D051186:Armadillo Domain Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D044842:Cullin Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D007814:Larva / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; C495267:CTNNB1 protein, mouse; C524852:Cul4 protein, Drosophila; C524851:Cul4B protein, mouse; D044842:Cullin Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; D051176:beta Catenin; D044767:Ubiquitin-Protein Ligases