Zipper-interacting protein kinase modulates canonical Wnt/beta-catenin signaling through interacting with Nemo-like kinase and T-cell factor 4

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 complex formation of NLK-T-cell factor (TCF) 4. 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.