TAB2 Scaffolds TAK1 and NLK in Repressing Canonical Wnt Signaling

	TAB2 Scaffolds TAK1 and NLK in Repressing Canonical Wnt Signaling
	Li, M; Wang, H; Huang, T; Wang, JY; Ding, Y; Li, ZF; Zhang, JK; Li, L
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2010
卷号	285 期号:18 页码:13397-13404
通讯作者	Li, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,lli@sibs.ac.cn
英文摘要	The TAK1-NLK cascade is a mitogen-activated protein kinase-related pathway that plays an inhibitory role in canonical Wnt/beta-catenin signaling through regulating the LEF1/TCF family transcriptional factors. TAB2 (TAK1-binding protein 2) is a putative TAK1 interacting protein that is involved in the regulation of TAK1. Here, we found that TAB2 could directly interact with NLK and function as a scaffold protein to facilitate the interaction between TAK1 and NLK. Knocking down TAB2 using small interfering RNA abolished the interaction of TAK1 with NLK in mammalian cells. The intermediate region (residues 292-417) of TAB2 was mapped for its binding to NLK. TAB2-Delta M, a TAB2 mutant lacking this region, showed a lower affinity for NLK and became defective in its scaffolding function. In addition, TAB2, but not TAB2-Delta M, mediated TAK1-dependent activation of NLK and LEF1 polyubiquitylation, resulting in the inhibition of canonical Wnt signaling. Moreover, Wnt3a stimulation led to an increase in the interaction of TAB2 with NLK and the formation of a TAK1.TAB2.NLK complex, suggesting that this TAK1-TAB2-NLK pathway may constitute a negative feedback mechanism for canonical Wnt signaling.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	NEMO-LIKE-KINASE ; MAP-KINASE ; KAPPA-B ; BETA-CATENIN ; POLYUBIQUITIN CHAINS ; MESODERM INDUCTION ; NEURAL INDUCTION ; PROTEIN-KINASES ; PATHWAY ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000276987700011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1085]
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	Li, M,Wang, H,Huang, T,et al. TAB2 Scaffolds TAK1 and NLK in Repressing Canonical Wnt Signaling[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2010,285(18):13397-13404.
APA	Li, M.,Wang, H.,Huang, T.,Wang, JY.,Ding, Y.,...&Li, L.(2010).TAB2 Scaffolds TAK1 and NLK in Repressing Canonical Wnt Signaling.JOURNAL OF BIOLOGICAL CHEMISTRY,285(18),13397-13404.
MLA	Li, M,et al."TAB2 Scaffolds TAK1 and NLK in Repressing Canonical Wnt Signaling".JOURNAL OF BIOLOGICAL CHEMISTRY 285.18(2010):13397-13404.