Tcf/Lef transcription factors during T-cell development: unique and overlapping functions.
Tcf/Lef transcription factors during T-cell development: unique and overlapping functions.
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DOI：
10.1038/sj.thj.6200001
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Clevers, H
中科院分区：
文献类型：
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作者：
Staal, F J;Clevers, H
TCF家族的创始成员是T细胞因子-1（Tcf-1）和淋巴增强因子-1（Lef-1）。在成年哺乳动物中，Tcf-1仅在T淋巴细胞中表达，而Lef-1在T细胞和早期B细胞中表达。然而，在小鼠发育过程中，Tcf-1和Lef-1的表达在许多组织中以复杂的重叠模式发生。Tcf-1和Lef-1的独特的体内功能已经通过基因破坏实验进行了探索。Tcf-1-/-敲除小鼠在T细胞生成方面严重受损，但其他方面正常。Lef-1-/-小鼠缺少毛发、牙齿、乳腺和三叉神经核，因此在出生前后死亡。从直接分析和移植实验中推断，Lef-1突变对免疫系统没有重大影响。在Tcf-1/Lef-1双基因敲除小鼠中，T细胞的发育被完全废除，表明Lef-1可以替代Tcf-1参与T细胞分化。TCF/LEF HMG结构域家族（TCF）的因子存在于整个动物界。很明显，TCF与脊椎动物Wnt效应子β-连环蛋白相互作用，介导非洲爪蟾中轴的形成。同样，Armadillo（β-连环蛋白的果蝇直系同源物）在无翅途径中位于果蝇TCF的遗传上游。在Wingless/Wnt信号传导后，Armadillo/β-连环蛋白与核TCF结合，并为所得的二分转录因子贡献反式激活结构域。在Wnt信号传导的情况下，Tcf因子与转录抑制因子的Groucho家族的蛋白质结合以强烈抑制靶基因转录。
The founding members of the TCF family are T-cell factor-1 (Tcf-1) and lymphoid enhancing factor-1 (Lef-1). In adult mammals, Tcf-1 is uniquely expressed in T lymphocytes, while Lef-1 is expressed in T cells and early B cells. During murine development, however, expression of Tcf-1 and Lef-1 occurs in complex overlapping patterns in many tissues. The unique in vivo function of Tcf-1 and Lef-1 have been explored by gene disruption experiments. Tcf-1-/- knockout mice are severely impaired in the generation of T cells, but are otherwise normal. Lef-1-/- mice lack hair, teeth, mammary glands and trigeminal nuclei and as a consequence die around birth. As deduced from direct analyses and from transplantation experiments, the Lef-1 mutation has no major effects on the immune system. In Tcf-1/Lef-1 double knockout mice, development of T cells is completely abrogated, indicating that Lef-1 can substitute for Tcf-1 in T-cell differentiation. Factors of the TCF/LEF HMG domain family (TCFs) exist throughout the animal kingdom. It has become evident that the TCFs interact with the vertebrate Wnt effector beta-catenin to mediate axis formation in Xenopus. Likewise, Armadillo (the Drosophila ortholog of beta-catenin) is genetically upstream of Drosophila TCF in the Wingless pathway. Upon Wingless/Wnt signaling, Armadillo/beta-catenin associate with nuclear TCFs and contribute a trans-activation domain to the resulting bipartite transcription factor. In the absence of Wnt signaling, Tcf factors associate with proteins of the Groucho family of transcriptional repressors to strongly repress target gene transcription.