清華大學生物膜與膜工程國家重點實驗室的陳曄光研究組以斑馬魚模型為基礎,，發(fā)現Dpr1作用Wnt信號途徑的又一新機制：Dpr1能同時調控細胞質和細胞核中的Wnt信號途徑,。
Dapper (Dpr)是近期發(fā)現的信號調控分子,，目前研究結果表明,，爪蟾和斑馬魚等低等動物的Dpr在早期胚胎發(fā)育的多個過程中起重要作用,，這些作用主要通過對 Wnt 和 Nodal/TGF-β 信號通路的負調控來完成,。Wnt和TGF-β 信號通路在胚胎發(fā)育和疾病發(fā)生過程中起著非常重要的作用,，因而 Dpr 可能是通過影響這些信號通路而參與生理,、病理過程,。
研究人員利用報告基因分析和體內斑馬魚胚胎分析，證明被迫定位于細胞核的Dpr1能對抗Wnt信號途徑：與β-catenin,，以及LEF1相互作用,，擾亂復合物的形成，而且Dpr1能與組蛋白去乙?；?相互作用,，增強LEF1與去乙酰化酶1之間的作用,。因此研究人員認為這說明Dpr1通過LEF1負調控了細胞核中Wnt信號途徑的基本活性,，從而得出結論：Dpr1能同時調控細胞質和細胞核中的Wnt信號途徑。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
