title: Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC-binding proteins, is a positive regulator of Wnt-β-catenin signalling.
abstract: The adenomatous polyposis coli (APC) membrane recruitment (Amer) family proteins Amer1/Wilms tumour gene on the X chromosome and Amer2 are binding partners of the APC tumour suppressor protein, and act as negative regulators in the Wnt signalling cascade. So far, nothing has been known about the third member of the family, Amer3. Here we show that Amer3 binds to the armadillo repeat domain of APC, similarly to Amer1 and Amer2. Amer3 also binds to the Wnt pathway regulator conductin/axin2. Furthermore, we identified Amer1 as binding partner of Amer3. Whereas Amer1 and Amer2 are linked to the plasma membrane by an N-terminal membrane localization domain, Amer3 lacks this domain. Amer3 localizes to the cytoplasm and nucleus of epithelial cells, and this is dependent on specific nuclear import and export sequences. Functionally, exogenous Amer3 enhances the expression of a β-catenin/T-cell factor-dependent reporter gene, and knockdown of endogenous Amer3 reduces Wnt target gene expression in colorectal cancer cells. Thus, Amer3 acts as an activator of Wnt signalling, in contrast to Amer1 and Amer2, which are inhibitors, suggesting a nonredundant role of Amer proteins in the regulation of this pathway. Our data, together with those of previous studies, provide a comprehensive picture of similarities and differences within the Amer protein family.
authors.affiliation: Nikolaus Fiebiger Centre for Molecular Medicine, University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Brauburger
authors.forename: Senem
authors.initials: S
authors.lastname: Akyildiz
authors.forename: Jan G
authors.initials: JG
authors.lastname: Ruppert
authors.forename: Michael
authors.initials: M
authors.lastname: Graeb
authors.forename: Dominic B
authors.initials: DB
authors.lastname: Bernkopf
authors.forename: Michel V
authors.initials: MV
authors.lastname: Hadjihannas
authors.forename: Jürgen
authors.initials: J
authors.lastname: Behrens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011125:Adenomatous Polyposis Coli / Q000378:metabolism*; D025601:Adenomatous Polyposis Coli Protein / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051186:Armadillo Domain Proteins / Q000737:chemistry / Q000378:metabolism; D060466:Axin Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D050505:Mutant Proteins; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals; D021381:Protein Transport; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway
chemical_list: C587666:AMER3 protein, human; C555337:APC protein, human; C491761:AXIN2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D051186:Armadillo Domain Proteins; D060466:Axin Protein; D050505:Mutant Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins
keywords: FAM123C; Wilms tumour gene on the X chromosome; Wnt signalling; adenomatous polyposis coli; adenomatous polyposis coli membrane recruitment 3