Roose J, Clevers H
Department of Immunology, Center for Biomedical Genetics, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands.
Biochim Biophys Acta. 1999 Oct 29;1424(2-3):M23-37. doi: 10.1016/s0304-419x(99)00026-8.
Although originally cloned as lymphoid transcription factors, members of the T-cell factor (Tcf) family are now well recognized as key activators/repressors in many developmental processes. Transcriptionally inert Tcf factors become potent transactivators upon interaction with the Wnt signaling product beta-catenin or its Drosophila counterpart Armadillo. In contrast, Tcf proteins mediate repression when bound to members of the Groucho family of transcriptional repressors, CBP and CtBP. Recently, Tcf factors have been reported as tumor inducers, aberrantly activating their target genes as a result of elevated beta-catenin levels in many types of cancer. These abnormal beta-catenin levels are usually caused by stabilizing mutations in beta-catenin itself or truncating mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. In this review, we will give a chronological overview of the Tcf factors and the phenotypes of Tcf mutant mice, as well as Tcf-binding partners. We will discuss Tcf signaling upon interaction with different partners, resulting in activator and repressor roles of Tcf factors in the light of carcinogenic events.
尽管最初作为淋巴样转录因子被克隆，但T细胞因子（Tcf）家族成员如今已被公认为许多发育过程中的关键激活因子/抑制因子。转录无活性的Tcf因子在与Wnt信号产物β-连环蛋白或其果蝇同源物犰狳相互作用后，会成为强大的反式激活因子。相反，当Tcf蛋白与转录抑制因子Groucho家族成员、CBP和CtBP结合时，会介导基因抑制。最近，有报道称Tcf因子是肿瘤诱导因子，在许多类型的癌症中，由于β-连环蛋白水平升高，它们会异常激活其靶基因。这些异常的β-连环蛋白水平通常是由β-连环蛋白自身的稳定突变或腺瘤性息肉病 coli（APC）肿瘤抑制基因的截短突变引起的。在这篇综述中，我们将按时间顺序概述Tcf因子、Tcf突变小鼠的表型以及Tcf结合伴侣。我们将讨论Tcf与不同伴侣相互作用时的信号传导，根据致癌事件阐述Tcf因子的激活和抑制作用。
