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

Authors

  • Misato Yamada,

    1. Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
    Search for more papers by this author
  • Bisei Ohkawara,

    1. Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
    Search for more papers by this author
  • Naoya Ichimura,

    1. Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
    Search for more papers by this author
  • Junko Hyodo-Miura,

    1. Division of Morphogenesis, Department of Developmental Biology, National institute for Basic Biology, Okazaki 444-8585, Japan
    Search for more papers by this author
  • Seiichi Urushiyama,

    Corresponding author
    1. Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
    Search for more papers by this author
  • Kyoko Shirakabe,

    1. Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
    Search for more papers by this author
  • Hiroshi Shibuya

    1. Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan
    Search for more papers by this author

  • Communicated by: Eisuke Nishida

*Correspondence: E-mail: urushi.mcb@mri.tmd.ac.jp

Abstract

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 β-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.

Ancillary