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	Dapper1 Is a Nucleocytoplasmic Shuttling Protein That Negatively Modulates Wnt Signaling in the Nucleus
	Gao, Xia ; Wen, Jun ; Zhang, Long ; Li, Xiang ; Ning, Yuanheng ; Meng, Anming ; Chen, Ye-Guang
	2010-10-12 ; 2010-10-12
关键词	APC TUMOR-SUPPRESSOR GLYCOGEN-SYNTHASE KINASE-3 BETA-CATENIN SUBCELLULAR-LOCALIZATION FUNCTIONAL INTERACTION XENOPUS EMBRYOS PATHWAY TCF TRANSCRIPTION REGULATOR Biochemistry & Molecular Biology
中文摘要	Wnt signaling, via the activation of the canonical beta-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 beta-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/beta-catenin signaling in the nucleus by keeping LEF1 in the repressive state. Thus, Dpr1 controls Wnt/beta-catenin signaling in both the cytoplasm and the nucleus.
语种	英语 ; 英语
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC ; BETHESDA ; 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/81770]
专题	清华大学
推荐引用方式 GB/T 7714	Gao, Xia,Wen, Jun,Zhang, Long,et al. Dapper1 Is a Nucleocytoplasmic Shuttling Protein That Negatively Modulates Wnt Signaling in the Nucleus[J],2010, 2010.
APA	Gao, Xia.,Wen, Jun.,Zhang, Long.,Li, Xiang.,Ning, Yuanheng.,...&Chen, Ye-Guang.(2010).Dapper1 Is a Nucleocytoplasmic Shuttling Protein That Negatively Modulates Wnt Signaling in the Nucleus..
MLA	Gao, Xia,et al."Dapper1 Is a Nucleocytoplasmic Shuttling Protein That Negatively Modulates Wnt Signaling in the Nucleus".(2010).

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