The ‘Down syndrome critical region’ is the segment of chromosome 21 that contains the genes responsible for the pathological features of Down syndrome. One of the genes located in this region encodes the dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), which is involved in the regulation of various cellular processes. On page , Pierre McCrea and colleagues now report a new link between DYRK1A and several Wnt target genes. Using Xenopus embryos, the authors identify p120-catenin (also known as catenin-δ1), especially isoform 1, as a new DYRK1A target and show that its phosphorylation on Thr47 by the kinase stabilises this member of the catenin family. The N-terminal region of p120-catenin is required for its association with DYRK1A. Furthermore, both proteins primarily interact in the nucleus, and DYRK1A overexpression relieves Kaiso-mediated repression of the Wnt target genes wnt11 and siamois. Expression of a phosphomimetic mutant p120-catenin in Xenopus embryos leads to increased levels of Wnt-11 and Siamois, and increases gastrulation defects. Together, these results highlight a new role for DYRK1A in p120-catenin–Kaiso signalling. In addition, they provide insight into a conceivable mechanism by which increased levels of DYRK1A that result from gene amplification in patients with Down syndrome could contribute to the pathophysiology of this disease.
