NLK-mediated phosphorylation of HDAC1 negatively regulates Wnt signaling

Research output: Contribution to journalArticle


The Wnt signaling pathway is essential in regulating various cellular processes. Different mechanisms of inhibition for Wnt signaling have been proposed. Besides β-catenin degradation through the proteasome, nemo-like kinase (NLK) is another molecule that is known to negatively regulate Wnt signaling. However, the mechanism by which NLK mediates the inhibition of Wnt signaling was not known. In the present study, we used primary embryonic fibroblast cells isolated from NLK-deficient mice and showed that these cells proliferate faster and have a shorter cell cycle than wild-type cells. In NLK-knockout cells, we observed sustained interaction between Lef1 and β-catenin, leading to elevated luciferase reporter of β-catenin/Lef1-mediated transcriptional activation. The mechanism for the reduced β-catenin/Lef1 promoter activation was explained by phosphorylation of HDAC1 at serine 421 via NLK. The phosphorylation of HDAC1 was achieved only in the presence of wild-type NLK because a catalytically inactive mutant of NLK was unable to phosphorylate HDAC1 and reduced the luciferase reporter of β-catenin/Lef1-mediated transcriptional activation. This result suggests that NLK and HDAC1 together negatively regulate Wnt signaling, which is vital in preventing aberrant proliferation of nontransformed primary fibroblast cells.


External organisations
  • Ningxia Medical University
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
  • Cancer and Oncology
Original languageEnglish
Pages (from-to)346-355
Number of pages10
JournalMolecular Biology of the Cell
Issue number2
Publication statusPublished - 2017 Jan 15
Publication categoryResearch