ARVCF is a novel Armadillo repeat domain protein that is closely related to the catenin p120ctn. Using new ARVCF monoclonal antibodies, we have found that ARVCF associates with E-cadherin and competes with p120 for interaction with the E-cadherin juxtamembrane

ARVCF (Armadillo repeat gene deleted in Velo-cardio-facial syndrome) is a candidate gene for the related developmental abnormalities Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) (Sirotkin et al., 1997), characterized by a wide spectrum of phenotypes such as conotruncal heart defects, cleft palate and facial dysmorphology (Shprintzen et al., 1981; Young et al., 1980). The gene maps to a region of human chromosome 22q11 (Bonne et al., 1998; Sirotkin et al., 1997) that is hemizygous in 80-85% of VCFS/DGS patients (Desmaze et al., 1993; Driscoll et al., 1993, 1992; Kelly et al., 1993; Morrow et al., 1995; Scambler et al., 1992; Wilson et al., 1992a,b). Other genes also map to this region and the contribution of the loss of ARVCF to these syndromes has not yet been fully established. ARVCF is the closest identified relative to the catenin p120ctn (‘p120’), suggesting that they have related functions (Sirotkin et al., 1997). Both proteins contain an amino-terminal coiled-coil domain, as well as a central Armadillo repeat domain (Arm domain). The Arm domains are 56% identical to one another and consist of 10 imperfect 42 amino acid repeats. Although the homology decreases in the aminoand carboxyterminal regions flanking the Arm repeats, the intron-exon structure of the genes is nearly identical (Keirsebilck et al., 1998), indicating an ancient evolutionary relationship. Alternative splicing results in the cell type-specific expression of multiple p120 isoforms whose individual roles are unknown (Keirsebilck et al., 1998; Mo and Reynolds, 1996). The cloned human ARVCF cDNA most closely resembles p120 isoform p120ctn1A (Reynolds and Daniel, 1997; Sirotkin et al., 1997). p120 interacts with a variety of cadherins, including E-, N-, P-, Cand VE-cadherins (Lampugnani et al., 1997; Reynolds et al., 1996; Yap et al., 1998). Cadherins are a large superfamily of transmembrane glycoproteins that mediate Ca2+-dependent cell-cell adhesion and participate in multiple aspects of development, morphogenesis and malignancy (for reviews, Takeichi, 1991; Yap, 1998). Of the classical cadherins, E-cadherin has been studied most extensively, in part because its expression is frequently downregulated or turned off in metastatic cancer (reviewed in Birchmeier and Behrens, 1994). It is the major cell-cell adhesion molecule in most carcinomas, and its downregulation in late-stage tumors is widely considered to be an important factor in the transition to malignancy. Indeed, restoration of E-cadherin expression in such cells restores adhesiveness and reduces invasive phenotypes both in vitro and in vivo (Frixen et al., 1991; Perl 1481 Journal of Cell Science 113, 1481-1490 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 JCS1224