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

PLoS One

Youngshin Lim¹  Ginam Cho¹  Jeffrey A. Golden¹  Il-Taeg Cho¹ 

[1] Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School Boston, Massachusetts, United States of America

关键词: Wnt signaling cascade;    Transcription factors;    Immunoprecipitation;    DNA-binding proteins;    Luciferase;    Stem cells;    Cell binding assay;    Neurological signaling;   

DOI  :  10.1371/journal.pone.0170282

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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/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.

【 授权许可】

CC BY