Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.
Physiological regulation of [beta]-catenin stability by Tcf3 and CK1epsilon.
复制标题
DOI：
10.1083/jcb.200102074
复制
发表时间：
2001-09-03
期刊：
影响因子：
--
通讯作者：
Kirschner MW
中科院分区：
文献类型：
--
作者：
Lee E;Salic A;Kirschner MW
wnt通路调节β-连环蛋白的稳态水平，β-连环蛋白是DNA结合蛋白Tcf 3/Lef 1家族的转录共激活因子。我们证明Tcf 3可以通过与轴蛋白和腺瘤性息肉病竞争β-catenin结合来抑制β-catenin更新。在非洲爪蟾胚胎和提取物中，不能结合Tcf 3的β-连环蛋白突变体比野生型蛋白降解得更快。β-catenin的片段和编码Tcf 4的NH 2末端的肽阻断β-catenin和Tcf 3之间的相互作用刺激β-catenin降解，表明这种相互作用通常在调节β-catenin周转中起重要作用。Tcf 3是糖原合成酶激酶（GSK）3和酪蛋白激酶（CK）1ε的底物，CKIε对Tcf 3的磷酸化刺激其与β-连环蛋白的结合，这一作用可被GSK 3逆转。Tcf 3与CK 1 ε协同抑制β-catenin降解，而CK 1 ε的抑制剂CKI-7降低Tcf 3的抑制作用。最后，我们提供的证据表明，CK 1 ε刺激凌乱（dsh）的GSK 3结合蛋白（GBP）的提取物中的结合。沿着大量的Tcf蛋白是非核的证据，这些发现表明CK 1 ε可以通过调节β-catenin-Tcf 3和GBP-dsh界面来调节体内wnt信号传导。
The wnt pathway regulates the steady state level of β-catenin, a transcriptional coactivator for the Tcf3/Lef1 family of DNA binding proteins. We demonstrate that Tcf3 can inhibit β-catenin turnover via its competition with axin and adenomatous polyposis for β-catenin binding. A mutant of β-catenin that cannot bind Tcf3 is degraded faster than the wild-type protein in Xenopus embryos and extracts. A fragment of β-catenin and a peptide encoding the NH2 terminus of Tcf4 that block the interaction between β-catenin and Tcf3 stimulate β-catenin degradation, indicating this interaction normally plays an important role in regulating β-catenin turnover. Tcf3 is a substrate for both glycogen synthase kinase (GSK) 3 and casein kinase (CK) 1ε, and phosphorylation of Tcf3 by CKIε stimulates its binding to β-catenin, an effect reversed by GSK3. Tcf3 synergizes with CK1ε to inhibit β-catenin degradation, whereas CKI-7, an inhibitor of CK1ε, reduces the inhibitory effect of Tcf3. Finally, we provide evidence that CK1ε stimulates the binding of dishevelled (dsh) to GSk3 binding protein (GBP) in extracts. Along with evidence that a significant amount of Tcf protein is nonnuclear, these findings suggest that CK1ε can modulate wnt signaling in vivo by regulating both the β-catenin-Tcf3 and the GBP-dsh interfaces.
登录
查看更多内容
影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
通讯作者：
Birchmeier, W
影响因子：
9.2
作者：
Hart, MJ;de los Santos, R;Polakis, P
通讯作者：
Polakis, P
影响因子：
4.8
作者：
Kishida, S;Yamamoto, H;Kikuchi, A
通讯作者：
Kikuchi, A
DOI：
10.1006/bbrc.2000.3607
发表时间：
2000-10-05
影响因子：
3.1
作者：
Julius, MA;Schelbert, B;Kitajewski, J
通讯作者：
Kitajewski, J
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R