T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with β-catenin to coactivate C/EBPα and steroidogenic factor 1 transcription factors
T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with β-catenin to coactivate C/EBPα and steroidogenic factor 1 transcription factors
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DOI：
10.1128/mcb.23.15.5366-5375.2003
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发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
MacDougald, OA
中科院分区：
文献类型：
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作者：
Kennell, JA;O'Leary, EE;MacDougald, OA
我们从发育中的垂体和3T3-L1前脂肪细胞中克隆了t细胞因子4N (TCF-4N)， TCF-4的另一种亚型。该蛋白含有-连环蛋白的n端相互作用结构域，但缺乏DNA结合结构域。虽然TCF- 4n抑制了TCF/淋巴细胞增强因子（LEF）依赖启动子的β -连环蛋白的共激活，但TCF- 4n增强了几种非TCF/LEF依赖启动子的β -连环蛋白的共激活。例如，TCF-4N通过与孤儿核受体甾体生成因子1 （SF-1）的功能和物理相互作用，与β -catenin协同激活α -抑制素启动子。此外，TCF-4N和β -连环蛋白与脂肪生成转录因子CCAAT/增强子结合蛋白α (C/EBPalpha)协同诱导瘦素启动子活性。基于这些重要转录调控因子之间的协同作用，β -连环蛋白和TCF-4N协同激活C/EBPalpha的机制似乎涉及p300。与TCF-4N重定向β -catenin在细胞中的作用一致，TCF-4N在3T3-L1前脂肪细胞中的异位表达部分缓解了β -catenin对脂肪形成的阻断。因此，我们提出TCF- 4n抑制TCF/LEF转录因子的β -catenin共激活，并增强其他转录因子（如SF-1和C/EBPalpha）的β -catenin共激活。
We have cloned T-cell factor 4N (TCF-4N), an alternative isoform of TCF-4, from developing pituitary and 3T3-L1 preadipocytes. This protein contains the N-terminal interaction domain for beta-catenin but lacks the DNA binding domain. While TCF-4N inhibited coactivation by beta-catenin of a TCF/lymphoid-enhancing factor (LEF)-dependent promoter, TCF-4N potentiated coactivation by beta-catenin of several non-TCF/LEF-dependent promoters. For example, TCF-4N synergized with beta-catenin to activate the alpha-inhibin promoter through functional and physical interactions with the orphan nuclear receptor steroidogenic factor 1 (SF-1). In addition, TCF-4N and beta-catenin synergized with the adipogenic transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) to induce leptin promoter activity. The mechanism by which beta-catenin and TCF-4N coactivated C/EBPalpha appeared to involve p300, based upon synergy between these important transcriptional regulators. Consistent with TCF-4N's redirecting the actions of beta-catenin in cells, ectopic expression of TCF-4N in 3T3-L1 preadipocytes partially relieved the block of adipogenesis caused by beta-catenin. Thus, we propose that TCF-4N inhibits coactivation by beta-catenin of TCF/LEF transcription factors and potentiates the coactivation by beta-catenin of other transcription factors, such as SF-1 and C/EBPalpha.