Nuclear translocation of αN-catenin by the novel zinc finger transcriptional repressor ZASC1

Alpha-catenins anchor the transmembrane cell-cell adhesion molecule E-cadherin indirectly to the actin cytoskeleton through interaction with β-catenin or plakoglobin. Three different α-catenins are known at present: αE-, αT-, and αN-catenin. Despite their different expression patterns, no functional differences between the α-catenins are known. In a yeast two-hybrid screening with αN-catenin as bait, we identified the Cys2-His2 zinc finger protein ZASC1. The mRNA and protein of ZASC1 were ubiquitously expressed in various cell lines and human tissues. Our results suggest an association of the ZASC1 protein with DNA, and luciferase reporter assays revealed that ZASC1 is a transcriptional repressor. Upon transient overexpression, the ZASC1 protein localized in the nucleus, to where it was able to recruit cytoplasmic αN-catenin. Neither the highly related αE-catenin nor αT-catenin interacted with ZASC1. By interchanging parts of αN-catenin and αE-catenin cDNAs, we were able to narrow down the interaction region of αN-catenin to two limited amino-terminal regions. On the other hand, the interaction of ZASC1 with αN-catenin can be mediated by the domain comprising zinc fingers six to eight of ZASC1. The interaction and nuclear cotranslocation of a neural α-catenin with a putative proto-oncogene product as reported here provides novel insights into the signaling functions of α-catenins.