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GENES CELLS (2003) 8, 677-684.
Copyright © 2003 Blackwell Publishing or its licensors



Original Article

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

M Yamada, B Ohkawara, N Ichimura, J Hyodo-Miura, S Urushiyama, K Shirakabe, and H Shibuya

BACKGROUND: Wnt signalling plays a critical role in many developmental processes and tumorigenesis. Wnt/beta-catenin signalling induces the stabilization of cytosolic beta-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/beta-catenin-induced axis duplication and expression of Wnt/beta-catenin target genes. Moreover, xHMG2L1 inhibited beta-catenin-stimulated transcriptional activity in mammalian cells. CONCLUSIONS: Our findings indicate that xHMG2L1 may negatively regulate Wnt/beta-catenin signalling, and that xHMG2L1 may play a role in early Xenopus development together with NLK.


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