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 beta-catenin or plakoglobin. Three different alpha-catenins are known at present: alpha E-, alpha T-, and alpha N-catenin. Despite their different expression patterns, no functional differences between the alpha-catenins are known.]it a yeast two-hybrid screening with aN-catenin as bait, we identified the Cys(2)-His(2) 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 ZASCI protein with DNA, and luciferase reporter assays revealed that ZASCI is a transcriptional repressor. Upon transient overexpression, the ZASCI protein localized in the nucleus, to where it was able to recruit cytoplasmic alpha N-catenin. Neither the highly related alpha E-catenin nor alpha T-catenin interacted with ZASC1. By interchanging parts of alpha N-catenin and alpha E-catenin cDNAs, we were able to narrow down the interaction region of alpha N-catenin to two limited amino-terminal regions. On the other hand, the interaction of ZASCI with alpha N-catenin can be mediated by the domain comprising zinc fingers six to eight of ZASC1. The interaction and nuclear cotranslocation of a neural alpha-catenin with a putative proto-oncogene product as reported here provides novel insights into the signaling functions of alpha-catenins. (c) 2005 Elsevier Inc. All rights reserved.