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

Misato Yamada1, Bisei Ohkawara, Naoya Ichimura

  • 1Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|July 24, 2003
PubMed
Abstract

Insights

Researchers identified HMG2L1 as a protein that interacts with NLK, a negative regulator of Wnt signaling. HMG2L1 inhibits Wnt/beta-catenin activity, suggesting a role in early development.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Signaling

Background:

  • Wnt signaling is crucial for development and cancer.
  • Wnt/beta-catenin pathway activation leads to target gene expression.
  • The MAP kinase pathway, including NLK, can counteract Wnt signaling.

Purpose of the Study:

  • To identify proteins that interact with NLK.
  • To investigate the role of HMG2L1 in Wnt/beta-catenin signaling.

Main Methods:

  • Yeast two-hybrid screening to identify NLK-interacting proteins.
  • mRNA injection into Xenopus embryos to assess HMG2L1 function.
  • Reporter gene assays in mammalian cells to measure transcriptional activity.

Main Results:

  • HMG2L1 was identified as an NLK-interacting protein.
  • Xenopus HMG2L1 (xHMG2L1) inhibited Wnt/beta-catenin-induced axis duplication in embryos.
  • xHMG2L1 suppressed Wnt/beta-catenin target gene expression and beta-catenin-stimulated transcription.

Conclusions:

  • HMG2L1 negatively regulates Wnt/beta-catenin signaling.
  • HMG2L1 may function with NLK in early Xenopus development.

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