NLK-mediated phosphorylation of HDAC1 negatively regulates Wnt signaling

Katarzyna Chmielarska Masoumi, Renée Daams, Wondossen Sime, Valentina Siino, Hengning Ke, Fredrik Levander, Ramin Massoumi

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

19 Citeringar (SciVal)


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.

Sidor (från-till)346-355
Antal sidor10
TidskriftMolecular Biology of the Cell
StatusPublished - 2017 jan. 15

Ämnesklassifikation (UKÄ)

  • Cell- och molekylärbiologi
  • Cancer och onkologi


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