Nuclear translocation of alphaN-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: alphaE-, alphaT-, and alphaN-catenin. Despite their different expression patterns, no functional differences between the alpha-catenins are known. In a yeast two-hybrid screening with alphaN-catenin as bait, we identified the Cys(2)-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 alphaN-catenin. Neither the highly related alphaE-catenin nor alphaT-catenin interacted with ZASC1. By interchanging parts of alphaN-catenin and alphaE-catenin cDNAs, we were able to narrow down the interaction region of alphaN-catenin to two limited amino-terminal regions. On the other hand, the interaction of ZASC1 with alphaN-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.
Bogaerts
Sven
S
Department for Molecular Biomedical Research, Molecular Cell Biology Unit, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent University, B-9052 Ghent, Belgium.
Vanlandschoot
Ann
A
van Hengel
Jolanda
J
van Roy
Frans
F
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D000090063:Proto-Oncogene Mas; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D016335:Zinc Fingers; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C486820:Ctnna2 protein, mouse; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; C479231:ZNF639 protein, human; D051178:alpha Catenin; D008156:Luciferases