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ZIPK modulates canonical Wnt/β‐catenin signaling through interaction with NLK/TCF4
Author(s) -
Togi Sumihito,
Muromoto Ryuta,
Matsuda Tadashi
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.734.1
Subject(s) - wnt signaling pathway , lrp6 , microbiology and biotechnology , wnt3a , beta catenin , catenin , signal transduction , biology , cancer research
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‐Tcell factor 4 (TCF4) complex. Importantly, ZIPK siRNA treatment in human colon carcinoma cells, in which Wnt/β‐catenin signaling was constitutively activated, 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.