{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n AMER3 is a member of the APC membrane recruitment (Amer) protein family, which also includes AMER1 (WTX) and AMER2. Unlike its family members that contain an N‐terminal membrane localization domain, AMER3 lacks this domain and instead localizes predominantly to the cytoplasm and nucleus via defined nuclear import and export signals. Functional studies have demonstrated that AMER3 binds to the armadillo repeat domain of APC and interacts with key regulators of the Wnt/β‐catenin pathway—including conductin/axin2 and AMER1—thereby acting as a positive modulator of Wnt signaling. In colorectal cancer cells, overexpression of AMER3 enhances β‐catenin/T‐cell factor–dependent transcription, whereas its knockdown results in reduced expression of Wnt target genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in Wnt pathway activation, genetic and genomic studies have implicated AMER3 in diverse biological processes. For example, microdeletions encompassing the AMER3 locus have been identified in patients with neurodevelopmental and neurobehavioral abnormalities, suggesting that loss of AMER3 may contribute to clinical phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, integrative bioinformatics analyses have nominated AMER3 as a candidate gene involved in adult neurogenesis in the hippocampus"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while epigenome‐wide studies indicate that methylation changes at an AMER3 CpG site can mediate the association between polycyclic aromatic hydrocarbon exposure and fasting plasma glucose, hinting at a metabolic role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Further evidence from cancer research suggests that AMER3 is subject to regulation by microRNAs; in colon cancer cells, for instance, modulation of the tumor suppressor let‐7f-5p altered AMER3 expression and impacted cell proliferation, thereby linking AMER3 to tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Finally, expression profiling during embryonic development reveals that, together with its paralogs, AMER3 is robustly expressed in both central and peripheral nervous systems as well as in other developing tissues, underlining its potential importance in organogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, AMER3 plays a nonredundant role within the Amer protein family by acting as a positive regulator of the Wnt/β‐catenin signaling pathway while also contributing to neurodevelopment, metabolic regulation, and oncogenic processes. This multifaceted functionality distinguishes AMER3 from other family members and highlights its potential involvement in diverse physiological and pathological contexts.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Katharina Brauburger, Senem Akyildiz, Jan G Ruppert, et al. 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