Disease relevance of CTNND2

• Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome [1].
• In this study, we report that a number of delta-catenin epitopes were expressed in human prostate cancer cells [2].
• Western blot and tissue microarray revealed a close association between increased delta-catenin expression and human primary prostatic adenocarcinomas [2].

High impact information on CTNND2

• By virtue of its restriction to the post-synaptic area, delta-catenin creates an asymmetric adherens junction in the region of the synapse [3].
• We report that delta-catenin interacts with cortactin in a tyrosine phosphorylation-dependent manner [4].
• We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree [4].
• Conversely, increasing tyrosine phosphorylation disrupts the delta-catenin-cortactin complex [4].
• Src family kinases can phosphorylate delta-catenin and bind to delta-catenin through its polyproline tract [4].

Biological context of CTNND2

• Mutagenesis and peptide competition experiments showed that the association of Erbin with the cadherin-catenin complex was mediated by the interaction of its PDZ domain with the C-terminal PDZ domain-binding motifs (DSWV-COOH) of ARVCF and delta-catenin [5].
• Delta-catenin is an adherens junction protein involved in cell motility and expressed early in neuronal development [1].
• By analyzing the same tumor cell clusters using consecutive sections, we showed that an increased delta-catenin immunoreactivity was accompanied by the down-regulation and redistribution of E-cadherin and p120ctn, major cell junction proteins whose inactivation is frequently associated with cancer progression [2].
• However, our recent analysis of the human genome revealed a consistent association of delta-catenin messenger RNA sequences with malignant cells, although the significance of these findings was unclear [2].
• We propose that delta-catenin can regulate adhesion molecules to implement the organization of large cellular arrays necessary for tissue morphogenesis [6].

Anatomical context of CTNND2

• The classical adherens junction that holds epithelial cells together consists of a protein complex in which members of the cadherin family linked to various catenins are the principal components. delta-catenin is a mammalian brain protein in the Armadillo repeat superfamily with sequence similarity to the adherens junction protein p120(ctn) [6].
• In developing mouse brain, staining with delta-catenin antibodies is prominent towards the apical boundary of the neuroepithelial cells in the ventricular zone [6].
• The ectopic expression of delta-catenin in MDCK cells altered their morphology, induced the elaboration of lamellipodia, interfered with monolayer formation, and increased scattering in response to hepatocyte growth factor treatment [6].
• We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, delta-catenin, and myogenic transcription factors at the neuromuscular junction [7].
• Antibodies against Kaiso and delta-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction [7].

Physical interactions of CTNND2

• Isolation of human delta-catenin and its binding specificity with presenilin 1 [8].
• Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses [9].
• Utilizing the cadherin membrane proximal region known to bind p120(ctn) and delta-catenin, coimmunoprecipitation experiments demonstrate that Xarvcf, likewise, binds cadherin in this region and that corresponding point mutations within conserved residues abrogate the Xarvcf-cadherin association [10].

Regulatory relationships of CTNND2

• In a purified system delta-catenin/NPRAP stimulated SPHK1 in a dose-dependent manner [11].

Other interactions of CTNND2

• We screened proteins for interaction with presenilin (PS) 1, and cloned the full-length cDNA of human delta-catenin, which encoded 1225 amino acids [8].
• Analysis of the interactions of the Erbin PDZ domain with synthetic peptides matching the C termini of ARVCF or delta-catenin also demonstrated specific high affinity binding [5].
• Finally, we showed that endogenous delta-catenin and Erbin co-localized in and co-immunoprecipitated from neurons [5].
• RESULTS.: DNA copy numbers of PRKAA1, CTNND2 and ERBIN were significantly different from normal controls (P < 0.05) [12].
• From co-immunoprecipitation analyses, the C-terminal portion of delta-catenin/NPRAP containing the seventh to tenth armadillo repeats was found to be required for interaction with SPHK1 [11].

Analytical, diagnostic and therapeutic context of CTNND2

• Furthermore, overexpression of delta-catenin in tumorigenic CWR-R1 cells that are derived from human prostate cancer xenograft resulted in reduced immunoreactivity for E-cadherin and p120ctn at the cell-cell junction [2].
• Therefore, we utilized the two hybrid system and confirmatory co-immunoprecipitations to identify a novel catenin, termed delta-catenin, which interacts with PS1 and is principally expressed in brain [13].

References