| First Author | Cho IT | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 1 | Pages | e0170282 |
| PubMed ID | 28103279 | Mgi Jnum | J:245963 |
| Mgi Id | MGI:5914243 | Doi | 10.1371/journal.pone.0170282 |
| Citation | Cho IT, et al. (2017) Aristaless Related Homeobox (ARX) Interacts with beta-Catenin, BCL9, and P300 to Regulate Canonical Wnt Signaling. PLoS One 12(1):e0170282 |
| abstractText | 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/beta-catenin signaling pathway, including beta-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/ beta-catenin signaling and that the C-terminal domain of ARX interacts with the armadillo repeats in beta-catenin to promote Wnt/beta-catenin signaling. In addition, we found BCL9 and P300 also interact with ARX to modulate Wnt/beta-catenin signaling. These data provide new insights into how ARX can uniquely regulate cortical neurogenesis, and connect the function of ARX with Wnt/beta-catenin signaling. |
