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Cullin4B/E3-ubiquitin ligase negatively regulates β-catenin

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Abstract

β-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, β-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 β-catenin levels. Loss-of-function mutation in Drosophila cul4 also shows increased β-catenin/Armadillo levels in developing embryos and displays a characteristic naked-cuticle phenotype. Immunoprecipitation experiments suggest that Cul4B and β-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 β-catenin levels.

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Abbreviations

CycE:

cyclin E

GSK-3:

glycogen synthase kinase-3

LEF:

lymphoid enhancing factor

RT-PCR:

reverse transcriptase-polymerase chain reaction

SCF:

Skp1, Cdc53/Cullin1, F-box protein

TCF:

T-cell factor

Wg:

Wingless

Wnt:

Wingless-type MMTV integration site family member

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India

    Rachana Tripathi, Satya Keerthi Kota & Usha K. Srinivas

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  1. Rachana Tripathi
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  2. Satya Keerthi Kota
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  3. Usha K. Srinivas
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Correspondence to Usha K. Srinivas.

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Tripathi, R., Kota, S.K. & Srinivas, U.K. Cullin4B/E3-ubiquitin ligase negatively regulates β-catenin. J. Biosci. 32 (Suppl 2), 1133–1138 (2007). https://doi.org/10.1007/s12038-007-0114-0

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  • DOI: https://doi.org/10.1007/s12038-007-0114-0

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