Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation

被引：600

作者：

Topol, L ^{[1
]}

Jiang, XY ^{[1
]}

Choi, H ^{[1
]}

Garrett-Beal, L ^{[1
]}

Carolan, PJ ^{[1
]}

Yang, YZ ^{[1
]}

机构：

[1] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA

来源：

JOURNAL OF CELL BIOLOGY | 2003年 / 162卷 / 05期

关键词：

limb; chondrogenesis; cancer; Siah2; APC;

D O I：

10.1083/jcb.200303158

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Writ as it does not signal by stabilizing beta-catenin in many biological systems. We have uncovered a new noncanonical pathway through which Wnt-5a antagonizes the canonical Writ pathway by promoting the degradation of beta-catenin. This pathway is Siah2 and APC dependent, but GSK-3 and beta-TrCP independent. Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote beta-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation.

引用

页码：899 / 908

页数：10

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