Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
J Biol Chem 2012 Jan 13;2873:1734-41. doi: 10.1074/jbc.M111.308650.
Show Gene links Show Anatomy links

Amer2 protein is a novel negative regulator of Wnt/β-catenin signaling involved in neuroectodermal patterning.

Pfister AS , Tanneberger K , Schambony A , Behrens J .

Wnt/β-catenin signaling is negatively controlled by the adenomatous polyposis coli (APC) tumor suppressor, which induces proteasomal degradation of β-catenin as part of the β-catenin destruction complex. Amer2 (APC membrane recruitment 2; FAM123A) is a direct interaction partner of APC, related to the tumor suppressor Amer1/WTX, but its function in Wnt signaling is not known. Here, we show that Amer2 recruits APC to the plasma membrane by binding to phosphatidylinositol 4,5-bisphosphate lipids via lysine-rich motifs and that APC links β-catenin and the destruction complex components axin and conductin to Amer2. Knockdown of Amer2 increased Wnt target gene expression and reporter activity in cell lines, and overexpression reduced reporter activity, which required membrane association of Amer2. In Xenopus embryos, Amer2 is expressed mainly in the dorsal neuroectoderm and neural tissues. Down-regulation of Amer2 by specific morpholino oligonucleotides altered neuroectodermal patterning, which could be rescued by expression of a dominant-negative mutant of Lef1 that interferes with β-catenin-dependent transcription. Our data characterize Amer2 for the first time as a negative regulator of Wnt signaling both in cell lines and in vivo and define Amer proteins as a novel family of Wnt pathway regulators.

PubMed ID: 22128170
PMC ID: PMC3265856
Article link: J Biol Chem

Species referenced: Xenopus laevis
Genes referenced: amer2 axin2l ctnnb1 egr2 en2 lef1 nodal3.1 rax sox2

Article Images: [+] show captions
References [+] :
Behrens, Functional interaction of beta-catenin with the transcription factor LEF-1. 1996, Pubmed, Xenbase