Notch post-translationally regulates β-catenin protein in stem and progenitor cells.
Notch post-translationally regulates β-catenin protein in stem and progenitor cells.
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DOI：
10.1038/ncb2313
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发表时间：
2011-08-14
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞自我更新或分化的决定来自于许多调节网络的整合和相互滴定。Notch和Wnt/β-Catenin信号传导通常在干细胞和祖细胞中交叉，并在转录上相互调节。通过每种途径的信号传导的生物学结果通常取决于细胞在分化阶段进展的背景和时机。在这里，我们表明膜结合的Notch与干细胞和结肠癌细胞中的未磷酸化（活性）β-连环蛋白物理缔合，并负调控活性β-连环蛋白蛋白的翻译后积累。Notch依赖性调节β-连环蛋白不需要Notch的配体依赖性膜切割或β-连环蛋白破坏复合物的糖原合酶激酶-3 β依赖性活性。然而，它确实需要内吞衔接蛋白Numb和溶酶体活性。这项研究揭示了Notch在负滴定干细胞和祖细胞中的活性β-连环蛋白水平中的先前未被认识的功能。
Cellular decisions of self-renewal or differentiation arise from integration and reciprocal titration of numerous regulatory networks. Notch and Wnt/β-Catenin signaling often intersect in stem and progenitor cells and regulate one another transcriptionally. The biological outcome of signaling through each pathway often depends on the context and timing as cells progress through stages of differentiation. Here, we show that membrane-bound Notch physically associates with unphosphorylated (active) β-Catenin in stem and colon cancer cells and negatively regulates post-translational accumulation of active β-Catenin protein. Notch-dependent regulation of β-Catenin protein did not require ligand-dependent membrane cleavage of Notch or the glycogen synthase kinase-3β-dependent activity of the β-catenin destruction complex. It did, however, require the endocytic adaptor protein, Numb, and lysosomal activity. This study reveals a previously unrecognized function of Notch in negatively titrating active β-Catenin protein levels in stem and progenitor cells.
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DOI：
10.1073/pnas.0704044104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Kwon, Chulan;Arnold, Joshua;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
影响因子：
21.3
作者：
Kwon, Chulan;Qian, Li;Cheng, Paul;Nigam, Vishal;Arnold, Joshua;Srivastava, Deepak
通讯作者：
Srivastava, Deepak
影响因子：
4.8
作者：
McGill, Melanie A.;Dho, Sascha E.;McGlade, C. Jane
通讯作者：
McGlade, C. Jane
影响因子：
64.8
作者：
Schroeter, EH;Kisslinger, JA;Kopan, R
通讯作者：
Kopan, R
影响因子：
--
作者：
Srinivas S;Watanabe T;Lin CS;William CM;Tanabe Y;Jessell TM;Costantini F
通讯作者：
Costantini F