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

Beitrag in einer Fachzeitschrift
(Originalarbeit)


Details zur Publikation

Autorinnen und Autoren: Pfister A, Tanneberger K, Schambony A, Behrens J
Zeitschrift: Journal of Biological Chemistry
Jahr der Veröffentlichung: 2012
Band: 287
Heftnummer: 3
Seitenbereich: 1734-1741
ISSN: 0021-9258


Abstract


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.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Behrens, Jürgen Prof. Dr.
Lehrstuhl für Experimentelle Medizin II (Molekulare Tumorforschung)
Schambony, Alexandra Prof. Dr.
Lehrstuhl für Entwicklungsbiologie


Zitierweisen

APA:
Pfister, A., Tanneberger, K., Schambony, A., & Behrens, J. (2012). Amer2 protein is a novel negative regulator of Wnt/β-catenin signaling involved in neuroectodermal patterning. Journal of Biological Chemistry, 287(3), 1734-1741. https://dx.doi.org/10.1074/jbc.M111.308650

MLA:
Pfister, Astrid, et al. "Amer2 protein is a novel negative regulator of Wnt/β-catenin signaling involved in neuroectodermal patterning." Journal of Biological Chemistry 287.3 (2012): 1734-1741.

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