Taxonomic distribution of proteins containing ARM domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing ARM domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Armadillo and dTCF: a marriage made in the nucleus.

Cavallo R, Rubenstein D, Peifer M
Curr Opin Genet Dev. 1997; 7: 459-66

Within the past year, Armadillo and beta-catenin's role in transducing the Wingless/Wnt signal has been substantially clarified. It is now clear that Armadillo and beta-catenin bind directly to members of the T-cell factor/lymphoid enhancer factor subfamily of HMG box DNA-binding proteins, forming bipartite transcription factors that regulate Wingless/Wnt responsive genes in both Drosophila and vertebrates. These partners not only play key roles in a variety of cell fate decisions during normal development but, when inappropriately activated, contribute to both colon cancer and melanoma.

Three-dimensional structure of the armadillo repeat region of beta-catenin.

Huber AH, Nelson WJ, Weis WI
Cell. 1997; 90: 871-82

Beta-catenin is essential for cadherin-based cell adhesion and Wnt/Wingless growth factor signaling. In these roles, it binds to cadherins, Tcf-family transcription factors, and the tumor suppressor gene product Adenomatous Polyposis Coli (APC). A core region of beta-catenin, composed of 12 copies of a 42 amino acid sequence motif known as an armadillo repeat, mediates these interactions. The three-dimensional structure of a protease-resistant fragment of beta-catenin containing the armadillo repeat region has been determined. The 12 repeats form a superhelix of helices that features a long, positively charged groove. Although unrelated in sequence, the beta-catenin binding regions of cadherins, Tcfs, and APC are acidic and are proposed to interact with this groove.

Signal transduction of beta-catenin.

Gumbiner BM
Curr Opin Cell Biol. 1995; 7: 634-40

Beta-catenin participates in signal transduction and developmental patterning in Xenopus and Drosophila embryos as a component of the Wnt signaling pathway. Its signaling activity is distinct from its role in cadherin-mediated cell adhesion, and it probably acts either in the cytosol or in the nucleus. The adenomatous polyposis coli tumor suppressor protein is also implicated in beta-catenin signaling.

Identification of plakoglobin domains required for association with N-cadherin and alpha-catenin.

Sacco PA, McGranahan TM, Wheelock MJ, Johnson KR
J Biol Chem. 1995; 270: 20201-6

Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule must be associated with the cytoskeleton via cytoplasmic proteins known as catenins. Three catenins, alpha-catenin, beta-catenin, and gamma-catenin (also known as plakoglobin), have been identified. The domain of the cadherin molecule important for its interaction with the catenins has been mapped to the COOH-terminal 70 amino acids, but less is known about regions of the catenins that allow them to associate with one another or with the cadherin molecule. In this study we have transfected carboxyl-terminal deletions of plakoglobin into the human fibrosarcoma HT-1080 and used immunofluorescence localization and co-immunoprecipitation to map the regions of plakoglobin that allow it to associate with N-cadherin and with alpha-catenin. Plakoglobin is an armadillo family member containing 13 weakly similar internal repeats. These data show that the alpha-catenin-binding region maps within the first repeat and the N-cadherin-binding region maps within repeats 7 and 8.

Association of the APC gene product with beta-catenin.

Rubinfeld B, Souza B, Albert I, Muller O, Chamberlain SH, Masiarz FR, Munemitsu S, Polakis P
Science. 1993; 262: 1731-4

Mutations in the human APC gene are linked to familial adenomatous polyposis and to the progression of sporadic colorectal and gastric tumors. To gain insight into APC function, APC-associated proteins were identified by immunoprecipitation experiments. Antibodies to APC precipitated a 95-kilodalton protein that was purified and identified by sequencing as beta-catenin, a protein that binds to the cell adhesion molecule E-cadherin. An antibody specific to beta-catenin also recognized the 95-kilodalton protein in the immunoprecipitates. These results suggest that APC is involved in cell adhesion.

Association of the APC tumor suppressor protein with catenins.

Su LK, Vogelstein B, Kinzler KW
Science. 1993; 262: 1734-7

Mutations of APC appear to initiate sporadic and inherited forms of human colorectal cancer. Although these mutations have been well characterized, little is known about the function of the APC gene product. Two cellular proteins that associate with APC were identified by nucleotide sequence analysis and peptide mapping as the E-cadherin-associated proteins alpha- and beta-catenin. A 27-residue fragment of APC containing a 15-amino acid repeat was sufficient for the interaction with the catenins. These results suggest an important link between tumor initiation and cell adhesion.

The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin.

Peifer M, Wieschaus E
Cell. 1990; 63: 1167-76

The Drosophila segment polarity gene armadillo is required for pattern formation within embryonic segments and imaginal discs. We have found that armadillo is highly conserved during evolution; it is 63% identical to human plakoglobin, a protein found in adhesive junctions joining epithelial and other cells. We have examined arm protein localization in a number of larval tissues and found that arm protein accumulation within cells shares many features with the accumulation of plakoglobin. We have compared the phenotype and molecular lesions responsible for the different arm mutations. Surprisingly, severely truncated proteins retain some function; the degree of function is strictly correlated with the length of the truncated protein, suggesting that the internally repetitive arm protein is modular in function. We present a possible model for the cellular role of arm.