GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com


Jump to: navigation, search


You don't have sufficient rights on this wiki to edit tables. Perhaps you need to log in. Changes you make in the Table editor will not be saved back to the wiki

See Help for Help on this wiki. See the documentation for how to use the table editor


Gao, X, Wen, J, Zhang, L, Li, X, Ning, Y, Meng, A and Chen, YG (2008) Dapper1 is a nucleocytoplasmic shuttling protein that negatively modulates Wnt signaling in the nucleus. J. Biol. Chem. 283:35679-88


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.


PubMed Online version:10.1074/jbc.M804088200


Active Transport, Cell Nucleus/drug effects; Active Transport, Cell Nucleus/physiology; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Animals; Antibiotics, Antineoplastic/pharmacology; Cell Nucleus/genetics; Cell Nucleus/metabolism; Cytoplasm/genetics; Cytoplasm/metabolism; Fatty Acids, Unsaturated/pharmacology; HeLa Cells; Histone Deacetylase 1; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Humans; Lymphoid Enhancer-Binding Factor 1/genetics; Lymphoid Enhancer-Binding Factor 1/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Signal Transduction/drug effects; Signal Transduction/physiology; Wnt1 Protein/genetics; Wnt1 Protein/metabolism; Zebrafish/genetics; Zebrafish/metabolism; beta Catenin/genetics; beta Catenin/metabolism