Identification of Zinc-finger BED Domain-containing 3 (Zbed3) as a Novel Axin-interacting Protein That Activates Wnt/beta-Catenin Signaling

	Identification of Zinc-finger BED Domain-containing 3 (Zbed3) as a Novel Axin-interacting Protein That Activates Wnt/beta-Catenin Signaling
	Chen, T; Li, M; Ding, Y; Zhang, LS; Xi, Y; Pan, WJ; Tao, DL; Wang, JY; Li, L
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2009
卷号	284 期号:11 页码:6683-6689
通讯作者	Li, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,lli@sibs.ac.cn
英文摘要	Axin, a key modulator of the Wnt/beta-catenin pathway, acts as a scaffold protein in phosphorylating and degrading cytoplasmic beta-catenin. Canonical Wnt proteins appear to stabilize beta-catenin by inducing the interaction of LRP5/6 with Axin. This interaction requires the phosphorylation of the Ser or Thr residues in the PPPP(S/T)PX(T/S) motifs at the intracellular domain of LRP5/6. In this work, we identified a novel Axin-interacting protein, zinc-finger BED domain-containing 3 (Zbed3), by yeast two-hybrid screening. The interaction was confirmed in co-immunoprecipitation experiment in mammalian cells and in vitro pulldown assays. Moreover, we found Zbed3 also contains a PPPPSPT motif, which is crucial to its binding to Axin. The Ser and Thr residues in the motif appear to be also phosphorylated by glycogen synthase kinase 3 beta (GSK3 beta) and the CKI family kinases, as GSK3 beta and CKI epsilon could enhance the interaction of Zbed3 with Axin. Mutation of the Ser (SA) or Thr (TA) residue to Ala in the motif markedly impaired its ability to interact with Axin. Expressing Zbed3, but not these mutants, led to inhibition of GSK3 beta-mediated beta-catenin phosphorylation, cytoplasmic beta-catenin accumulation, and activation of lymphoid enhancer binding factor-1-dependent reporter gene transcription. Furthermore, knockdown of Zbed3 with RNA interference attenuated Wnt-induced beta-catenin accumulation, lymphoid enhancer binding factor-1-dependent luciferase reporter activity, and the Wnt target gene expression. These results together indicate that Zbed3 is a novel Axin-binding protein that is involved in Wnt/beta-catenin signaling modulation.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	DUAL-KINASE MECHANISM ; BETA-CATENIN ; NEGATIVE REGULATOR ; WNT ; PATHWAY ; PHOSPHORYLATION ; COMPLEX ; TRANSDUCTION ; EXPRESSION ; STABILITY
收录类别	SCI
语种	英语
WOS记录号	WOS:000263919000012
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1260]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Chen, T,Li, M,Ding, Y,et al. Identification of Zinc-finger BED Domain-containing 3 (Zbed3) as a Novel Axin-interacting Protein That Activates Wnt/beta-Catenin Signaling[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2009,284(11):6683-6689.
APA	Chen, T.,Li, M.,Ding, Y.,Zhang, LS.,Xi, Y.,...&Li, L.(2009).Identification of Zinc-finger BED Domain-containing 3 (Zbed3) as a Novel Axin-interacting Protein That Activates Wnt/beta-Catenin Signaling.JOURNAL OF BIOLOGICAL CHEMISTRY,284(11),6683-6689.
MLA	Chen, T,et al."Identification of Zinc-finger BED Domain-containing 3 (Zbed3) as a Novel Axin-interacting Protein That Activates Wnt/beta-Catenin Signaling".JOURNAL OF BIOLOGICAL CHEMISTRY 284.11(2009):6683-6689.