MOLECULAR-CLONING OF THE HUMAN P120(CTN) CATENIN GENE (CTNND1) - EXPRESSION OF MULTIPLE ALTERNATIVELY SPLICED ISOFORMS

Catenins were discovered as proteins that are linked to the cytoplasmi c domain of transmembrane cadherins. Among these junctional plaque pro teins are several members of the Armadillo gene family: beta-catenin, plakoglobin, and p120(ctn). Recently it became clear that some catenin s also mediate nuclear signaling. We performed a detailed analysis of the human p120(ctn) gene (HGMW-approved symbol CTNND1) and its transcr ipts. The human p120(ctn) gene comprises 21 exons, potentially encodin g up to 32 protein isoforms as products of alternative splicing. Human isoforms, designated 1 to 4, differ from each other by the start codo n used. Additional isoforms are derived from combinations with alterna tively used exons A (exon 18) and B (20), near the end of the open rea ding frame, and also with exon C (11) in the middle of the open readin g frame. Hence, the longest isoform is of type 1ABC and comprises 968 amino acid residues. The functional consequence of the observed multit ude of p120(ctn) splice variants awaits further study, but tissue-spec ific expression was obvious. Further, we demonstrate that the exon org anization, which is not simply related to the Armadillo repeat structu re, is very well conserved between the p120(ctn) gene and the related ARVCF gene, but not at all between these two genes and the beta-cateni n or plakoglobin genes. The present data favor the concept that p1200( ctn) is the prototype of a subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP, and plakophilins 1 and 2, that are more related to each other than to other Armadillo proteins. (C) 1998 Academic Press.