Tripathi Rachana, Kota Satya Keerthi, Srinivas Usha K
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
J Biosci. 2007 Sep;32(6):1133-8. doi: 10.1007/s12038-007-0114-0.
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.
β-连环蛋白是无翅型MMTV整合位点家族成员（Wnt）信号的关键转导因子，其上调是结肠癌和其他组织癌症的病因。在没有Wnt信号的情况下，β-连环蛋白会被靶向泛素-蛋白酶体介导的降解。在此，我们展示了由cul4B编码的E3泛素连接酶的功能特性。在小鼠细胞系C3H T10（1/2）中，RNA干扰介导的Cul4B敲低导致β-连环蛋白水平升高。果蝇cul4中的功能丧失突变也显示，发育中的胚胎中β-连环蛋白/犰狳蛋白水平升高，并表现出特征性的裸表皮表型。免疫沉淀实验表明，Cul4B和β-连环蛋白是果蝇、小鼠和人类信号复合物的一部分。这些初步结果表明，Cul4B在调节β-连环蛋白水平方面具有保守作用。
