Cho, Il-TaegLim, YoungshinGolden, JeffreyCho, Ginam2017-03-282017Cho, Il-Taeg, Youngshin Lim, Jeffrey A. Golden, and Ginam Cho. 2017. “Aristaless Related Homeobox (ARX) Interacts with β-Catenin, BCL9, and P300 to Regulate Canonical Wnt Signaling.” PLoS ONE 12 (1): e0170282. doi:10.1371/journal.pone.0170282. http://dx.doi.org/10.1371/journal.pone.0170282.http://nrs.harvard.edu/urn-3:HUL.InstRepos:31731657Mutations in the Aristaless Related Homeobox (ARX) gene are associated with a spectrum of structural (lissencephaly) and functional (epilepsy and intellectual disabilities) neurodevelopmental disorders. How mutations in this single transcription factor can result in such a broad range of phenotypes remains poorly understood. We hypothesized that ARX functions through distinct interactions with specific transcription factors/cofactors to regulate unique target genes in different cell types. To identify ARX interacting proteins, we performed an unbiased proteomics screen and identified several components of the Wnt/β-catenin signaling pathway, including β-catenin (CTNNB1), B-cell CLL/lymphoma 9 (BCL9) and leucine rich repeat flightless interacting protein 2 (LRRFIP2), in cortical progenitor cells. Our data show that ARX positively regulates Wnt/ β-catenin signaling and that the C-terminal domain of ARX interacts with the armadillo repeats in β-catenin to promote Wnt/β-catenin signaling. In addition, we found BCL9 and P300 also interact with ARX to modulate Wnt/β-catenin signaling. These data provide new insights into how ARX can uniquely regulate cortical neurogenesis, and connect the function of ARX with Wnt/β-catenin signaling.en-USBiology and Life SciencesCell BiologySignal TransductionCell SignalingSignaling CascadesWNT Signaling CascadeBiology and life sciencesBiochemistryProteinsDNA-binding proteinsTranscription FactorsGeneticsGene ExpressionGene RegulationRegulatory ProteinsPrecipitation TechniquesImmunoprecipitationGene expressionDNA transcriptionCellular TypesAnimal CellsStem CellsEnzymologyEnzymesOxidoreductasesLuciferaseNeurological SignalingJournal Article2017-03-2810.1371/journal.pone.0170282