Seidensticker M J, Behrens J
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13122, Berlin, Germany.
Biochim Biophys Acta. 2000 Feb 2;1495(2):168-82. doi: 10.1016/s0167-4889(99)00158-5.
The wnt signal transduction pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. The cytoplasmic component beta-catenin is central to the transmission of wnt signals to the nucleus: in the absence of wnts beta-catenin is constitutively degraded in proteasomes, whereas in the presence of wnts beta-catenin is stabilized and associates with HMG box transcription factors of the LEF/TCF family. In tumors, beta-catenin degradation is blocked by mutations of the tumor suppressor gene APC (adenomatous polyposis coli), or of beta-catenin itself. As a consequence, constitutive TCF/beta-catenin complexes are formed and activate oncogenic target genes. This review discusses the mechanisms that silence the pathway in cells that do not receive a wnt signal and goes on to describe the regulatory steps involved in the activation of the pathway.
Wnt信号转导通路参与胚胎发育过程中的许多分化事件，其组分异常激活后可导致肿瘤形成。细胞质组分β-连环蛋白是Wnt信号向细胞核传递的核心：在没有Wnt的情况下，β-连环蛋白在蛋白酶体中持续降解，而在有Wnt的情况下，β-连环蛋白被稳定化并与LEF/TCF家族的HMG盒转录因子结合。在肿瘤中，肿瘤抑制基因APC（腺瘤性息肉病 coli）或β-连环蛋白本身的突变会阻止β-连环蛋白的降解。因此，组成型TCF/β-连环蛋白复合物形成并激活致癌靶基因。本综述讨论了在未接收到Wnt信号的细胞中使该通路沉默的机制，并继续描述该通路激活过程中涉及的调节步骤。
