All Tcf HMG box transcription factors interact with Groucho-related co-repressors
All Tcf HMG box transcription factors interact with Groucho-related co-repressors
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DOI：
10.1093/nar/29.7.1410
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发表时间：
2001-04-01
影响因子：
14.9
通讯作者：
Clevers, H
中科院分区：
文献类型：
--
作者：
Brantjes, H;Roose, J;Clevers, H
Tcf/Lef家族转录因子是Wingless/Wnt信号转导通路的下游效应因子。在无Wingless/Wnt信号传导过程中，β -catenin易位到细胞核，与Tcf相互作用（1-3），从而激活靶基因的转录（4,5），Tcf因子还与Groucho （Grg/TLE）转录共抑制因子家族成员相互作用(6)。我们现在已经测试了所有已知的哺乳动物Groucho家族成员与Tcf/Lef家族成员特异性相互作用的能力。在报告细胞实验中，任何Tcf的转录激活都可以被Grg-1、Grg-2/TLE-2、Grg-3和Grg-4抑制。Tcf和Grg蛋白之间的特异性相互作用可以通过组织或细胞类型受限的表达在体内实现。为了解决这个问题，我们在一组细胞系中测定了所有Tcf和Grg/TLE家族成员的表达。在任何细胞系中，多个tfs和TLEs都是共表达的。因此，Tcf/Grg交互中的冗余似乎是规则。含有五个结构域的“长”格劳乔家族成员是tcf介导的转激活的抑制因子，而只包含前两个结构域的Grg-5作为去抑制因子。正如之前在果蝇格劳乔中所显示的那样，我们发现长Grg蛋白与组蛋白去乙酰酶-1相互作用。尽管Grg-5含有介导长Grg蛋白中HDAC结合的GP同源结构域，但Grg-5不能结合这种共抑制因子，这解释了它如何去抑制转录。
Tcf/Lef family transcription factors are the downstream effecters of the Wingless/Wnt signal transduction pathway. Upon Wingless/Wnt signalling, beta -catenin translocates to the nucleus, interacts with Tcf (1-3) and thus activates transcription of target genes (4,5), Tcf factors also interact with members of the Groucho (Grg/TLE) family of transcriptional co-repressors (6), We have now tested all known mammalian Groucho family members for their ability to interact specifically with individual Tcf/Lef family members. Transcriptional activation by any Tcf could be repressed by Grg-1, Grg-2/TLE-2, Grg-3 and Grg-4 in a reporter assay. Specific interactions between Tcf and Grg proteins may be achieved in vivo by tissue- or cell type-limited expression. To address this, we determined the expression of all Tcf and Grg/TLE family members in a panel of cell lines. Within any cell line, several Tcfs and TLEs are co-expressed. Thus, redundancy in Tcf/Grg interactions appears to be the rule. The 'long' Groucho family members containing five domains are repressors of Tcf-mediated transactivation, whereas Grg-5, which only contains the first two domains, acts as a de-repressor, As previously shown for Drosophila Groucho, we show that long Grg proteins interact with histone deacetylase-1. Although Grg-5 contains the GP homology domain that mediates HDAC binding in long Grg proteins, Grg-5 fails to bind this co-repressor, explaining how it can de-repress transcription.