DIPA is a novel, isoform-specific binding partner of the tumor-associated p120 isoform 1

Abstract

p120-catenin (p120) is a master regulator of cellular adherens junctions and is important for epithelial homeostasis, development, tumorigenesis, and metastasis. Relatively little is known about the different functions of p120 isoforms. During validation of a yeast two-hybrid screen using p120 as bait, I detected an isoform-specific interaction with Delta-Interacting Protein A (DIPA). In this study, I show that DIPA co-localizes and co-immunoprecipitates reciprocally with the long p120-1 isoform, but not the shorter p120-3 isoform, which lacks an N-terminal head domain. Also, p120-1 expression is required for the plasma membrane localization of DIPA. The p120 family members ARVCF, p0071, and δ-catenin have similar N-terminal regions to p120-1 and also bind to DIPA, suggesting that the interaction is highly conserved. These family members can recruit DIPA to the plasma membrane in the absence of p120-1. DIPA is the first protein discovered to selectively interact with isoform p120-1, and my data suggest that their relationship is potentially important for a novel, cell contact mediated function.