ZIPK modulates canonical Wnt/β‐catenin signaling through interaction with NLK/TCF4

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.