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XB-ART-4960

Genes Cells. August 1, 2003; 8 (8):

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

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

Abstract

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.

Pubmed Id: 12875653

Article link: Genes Cells.

Genes referenced: hmgxb4 lef1 map3k7 mapk1 nlk nlk.2 nr2c2

Antibodies referenced: