β-catenin 转录激活复合物的失活
中文名称
通路描述
下调 TCF 依赖性转录涉及的机制尚未完全清楚。β-catenin 已知招募 Reptin、SMRT 和 NCoR 等转录抑制物到 TCF/LEF 复合物，使转录从激活转变为抑制（Bauer et al, 2000; Weiske et al, 2007; Song and Gelmann, 2008）。CTNNBIP1（也称为 ICAT）和 Chibby 是 TCF 依赖性信号传导的抑制剂，它们通过直接结合β-catenin 并阻止其与转录激活机器中的关键成分相互作用而发挥作用（Takemaru et al, 2003; Li et al, 2008; Tago et al, 2000; Graham et al, 2002; Daniels and Weiss, 2002）。Chibby 还促进β-catenin 的核输出，并与 14-3-3/YWHAZ 蛋白一起（Takemura et al, 2003; Li et al, 2008）。最近的一些研究还表明核 APC 在β-catenin 激活复合物的解聚中发挥作用（Hamada and Bienz, 2004; Sierra et al, 2006）。值得注意的是，虽然参与β-catenin 转录激活复合物解聚的一些参与者正在体外研究中取得进展，但它们在体内的意义尚未完全清楚，并且有些可以被敲除而对内源性 WNT 信号传导几乎没有影响（例如 Voronina et al, 2009）。
英文描述
Deactivation of the beta-catenin transactivating complex The mechanisms involved in downregulation of TCF-dependent transcription are not yet very well understood. beta-catenin is known to recruit a number of transcriptional repressors, including Reptin, SMRT and NCoR, to the TCF/LEF complex, allowing the transition from activation to repression (Bauer et al, 2000; Weiske et al, 2007; Song and Gelmann, 2008). CTNNBIP1 (also known as ICAT) and Chibby are inhibitors of TCF-dependent signaling that function by binding directly to beta-catenin and preventing interactions with critical components of the transactivation machinery (Takemaru et al, 2003; Li et al, 2008; Tago et al, 2000; Graham et al, 2002; Daniels and Weiss, 2002). Chibby additionally promotes the nuclear export of beta-catenin in conjunction with 14-3-3/YWHAZ proteins (Takemura et al, 2003; Li et al, 2008). A couple of recent studies have also suggested a role for nuclear APC in the disassembly of the beta-catenin activation complex (Hamada and Bienz, 2004; Sierra et al, 2006). It is worth noting that while some of the players involved in the disassembly of the beta-catenin transactivating complex are beginning to be worked out in vitro, the significance of their role in vivo is not yet fully understood, and some can be knocked out with little effect on endogenous WNT signaling (see for instance Voronina et al, 2009).
所含基因
44 个基因