title: Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4).
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.
authors: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors: Sumihito
authors: S
authors: Togi
authors: Osamu
authors: O
authors: Ikeda
authors: Shinya
authors: S
authors: Kamitani
authors: Misa
authors: M
authors: Nakasuji
authors: Yuichi
authors: Y
authors: Sekine
authors: Ryuta
authors: R
authors: Muromoto
authors: Asuka
authors: A
authors: Nanbo
authors: Kenji
authors: K
authors: Oritani
authors: Taro
authors: T
authors: Kawai
authors: Shizuo
authors: S
authors: Akira
authors: Tadashi
authors: T
authors: Matsuda
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D064550:Death-Associated Protein Kinases; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C470551:NLK protein, human; D064550:Death-Associated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases