Aristaless Related Homeobox (ARX) Interacts with ß-Catenin, BCL9, and P300 to Regulate Canonical Wnt Signaling.
PLoS One
; 12(1): e0170282, 2017.
Article
em En
| MEDLINE
| ID: mdl-28103279
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/ß-catenin signaling pathway, including ß-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/ ß-catenin signaling and that the C-terminal domain of ARX interacts with the armadillo repeats in ß-catenin to promote Wnt/ß-catenin signaling. In addition, we found BCL9 and P300 also interact with ARX to modulate Wnt/ß-catenin signaling. These data provide new insights into how ARX can uniquely regulate cortical neurogenesis, and connect the function of ARX with Wnt/ß-catenin signaling.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas de Homeodomínio
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Proteína p300 Associada a E1A
/
Beta Catenina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos