Negative regulation of Wnt signalling by HMG2L1, a novel NLK-binding protein

Background: Wnt signalling plays a critical role in many developmental processes and tumorigenesis. Wnt/β-catenin signalling induces the stabilization of cytosolic β-catenin, which interacts with TCF/LEF-1 transcription factors, thereby inducing expression of Wnt-target genes. Recent evidence suggests that a specific MAP kinase pathway involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt signalling. Results: To identify NLK-interacting proteins, we performed yeast two-hybrid screening. We isolated the gene HMG2L1 and showed that injection of Xenopus HMG2L1 (xHMG2L1) mRNA into Xenopus embryos inhibited Wnt/β-catenin-induced axis duplication and expression of Wnt/β-catenin target genes. Moreover, xHMG2L1 inhibited 5-catenin-stimulated transcriptional activity in mammalian cells. Conclusions: Our findings indicate that xHMG2L1 may negatively regulate Wnt/β-catenin signalling, and that xHMG2L1 may play a role in early Xenopus development together with NLK.