Abstract
Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in apoptosis and transcriptional regulation. Here, we identified Nemo-like kinase (NLK) as a novel ZIPK-binding partner and found that ZIPK regulates NLK-mediated repression of canonical Wnt/β-catenin signaling. Indeed, siRNA-mediated reduction of endogenous ZIPK expression reduced Wnt/β-catenin signaling. Furthermore, ZIPK affected the formation of NLK-T-cell factor 4 (TCF4) complex. Importantly, ZIPK siRNA treatment in human colon carcinoma cells resulted in a reduction of β-catenin/TCF-mediated gene expression and cell growth. These results indicate that ZIPK may serve as a transcriptional regulator of canonical Wnt/β-catenin signaling through interaction with NLK/TCF4.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Death-Associated Protein Kinases
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Gene Expression Regulation / physiology
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HeLa Cells
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism
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Protein Binding / physiology
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Signal Transduction / physiology*
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Transcription Factor 4
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / physiology
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Wnt Proteins / genetics
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Wnt Proteins / metabolism*
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Apoptosis Regulatory Proteins
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Intracellular Signaling Peptides and Proteins
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Multiprotein Complexes
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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Wnt Proteins
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beta Catenin
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NLK protein, human
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Death-Associated Protein Kinases
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Protein Serine-Threonine Kinases
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Calcium-Calmodulin-Dependent Protein Kinases