清华大学生物膜与膜工程国家重点实验室的陈晔光研究组以斑马鱼模型为基础，发现Dpr1作用Wnt信号途径的又一新机制：Dpr1能同时调控细胞质和细胞核中的Wnt信号途径。
Dapper (Dpr)是近期发现的信号调控分子，目前研究结果表明，爪蟾和斑马鱼等低等动物的Dpr在早期胚胎发育的多个过程中起重要作用，这些作用主要通过对 Wnt 和 Nodal/TGF-β 信号通路的负调控来完成。Wnt和TGF-β 信号通路在胚胎发育和疾病发生过程中起着非常重要的作用，因而 Dpr 可能是通过影响这些信号通路而参与生理、病理过程。
研究人员利用报告基因分析和体内斑马鱼胚胎分析，证明被迫定位于细胞核的Dpr1能对抗Wnt信号途径：与β-catenin，以及LEF1相互作用，扰乱复合物的形成，而且Dpr1能与组蛋白去乙酰化酶1相互作用，增强LEF1与去乙酰化酶1之间的作用。因此研究人员认为这说明Dpr1通过LEF1负调控了细胞核中Wnt信号途径的基本活性，从而得出结论：Dpr1能同时调控细胞质和细胞核中的Wnt信号途径。（生物谷Bioon.com）
生物谷推荐原始出处：
J. Biol. Chem., Vol. 283, Issue 51, 35679-35688, December 19, 2008
Dapper1 Is a Nucleocytoplasmic Shuttling Protein That Negatively Modulates Wnt Signaling in the Nucleus*
Xia Gao, Jun Wen, Long Zhang, Xiang Li, Yuanheng Ning, Anming Meng, and Ye-Guang Chen1
From the State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China
Wnt signaling, via the activation of the canonical β-catenin and lymphoid enhancer factor (LEF)/T-cell factor pathway, plays an important role in embryogenesis and cancer development by regulating the expression of genes involved in cell proliferation, differentiation, and survival. Dapper (Dpr), as a Dishevelled interactor, has been suggested to modulate Wnt signaling by promoting Dishevelled degradation. Here, we provide evidence that Dpr1 shuttles between the cytoplasm and the nucleus. Although overexpressed Dpr1 was mainly found in the cytoplasm, endogenous Dpr1 was localized over the cell, and Wnt1 induced its nuclear export. Treatment with leptomycin B induced nuclear accumulation of both endogenous and overexpressed Dpr1. We further identified the nuclear localization signal and the nuclear export signal within Dpr1. Using reporter assay and in vivo zebrafish embryo assay, we demonstrated that the forced nuclearly localized Dpr1 possessed the ability to antagonize Wnt signaling. Dpr1 interacted with β-catenin and LEF1 and disrupted their complex formation. Furthermore, Dpr1 could associate with histone deacetylase 1 (HDAC1) and enhance the LEF1-HDAC1 interaction. Together, our findings suggest that Dpr1 negatively modulates the basal activity of Wnt/β-catenin signaling in the nucleus by keeping LEF1 in the repressive state. Thus, Dpr1 controls Wnt/β-catenin signaling in both the cytoplasm and the nucleus.
