Aristaless Related Homeobox (ARX) Interacts with ?-Catenin, BCL9, and P300 to Regulate Canonical Wnt Signaling.

ABSTRACT: Mutations 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/?-catenin signaling pathway, including ?-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/ ?-catenin signaling and that the C-terminal domain of ARX interacts with the armadillo repeats in ?-catenin to promote Wnt/?-catenin signaling. In addition, we found BCL9 and P300 also interact with ARX to modulate Wnt/?-catenin signaling. These data provide new insights into how ARX can uniquely regulate cortical neurogenesis, and connect the function of ARX with Wnt/?-catenin signaling.

SUBMITTER: Cho IT 

PROVIDER: S-EPMC5245867 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature