Barker N, Clevers H
University Medical Center Utrecht, Department of Immunology, The Netherlands.
Bioessays. 2000 Nov;22(11):961-5. doi: 10.1002/1521-1878(200011)22:11<961::AID-BIES1>3.0.CO;2-T.
Recent studies indicate that plakoglobin may have a similar function to that of beta-catenin within the Wnt signaling pathway. beta-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs(1) and coworkers show, however, that unlike beta-catenin, plakoglobin induces neoplastic transformation of rat epithelial cells in the absence of such stabilizing mutations. Cellular transformation by plakoglobin also appears to be distinct from that of beta-catenin in that it requires activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than beta-catenin, despite its previous identification as a target of Tcf/beta-catenin.(2) In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by beta-catenin than plakoglobin. Plakoglobin and beta-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity.
近期研究表明，在Wnt信号通路中，桥粒芯蛋白可能具有与β-连环蛋白类似的功能。已知在获得氨基末端序列的稳定突变后，β-连环蛋白在多种人类癌症中是一种癌基因。然而，科利格斯等人（1）发现，与β-连环蛋白不同，桥粒芯蛋白在没有此类稳定突变的情况下可诱导大鼠上皮细胞发生肿瘤转化。桥粒芯蛋白引起的细胞转化似乎也与β-连环蛋白不同，因为它需要原癌基因c-myc的激活。令人惊讶的是，尽管c-myc先前被确定为Tcf/β-连环蛋白的靶点（2），但桥粒芯蛋白比β-连环蛋白更有效地激活c-myc。相比之下，合成的Tcf报告基因被β-连环蛋白激活的程度比桥粒芯蛋白大得多。因此，桥粒芯蛋白和β-连环蛋白在Wnt信号传导和癌症中可能具有不同的作用，这反映了它们对靶基因活性的不同影响。
