Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catenins (alpha-, beta- and gamma- or plakoglobin) are cytoplasmic cadherin-associated proteins. Studies on cultured cells have suggested that both alpha-catenin and plakoglobin are important for the adhesive function of cadherins. alpha-catenin binds to both beta-catenin and plakoglobin and may link the cadherin/catenin complex to actin filaments. Separate domains of plakoglobin bind to cadherin and alpha-catenin, suggesting it may act as a bridge between these molecules. However, plakoglobin may have other activities: it is expressed in both desmosomal junctions in association with desmogleins and the cytoplasm in conjunction with APC, and previous work suggests it may act in a dorsal signalling pathway when overexpressed in Xenopus embryos. Here, we have studied the roles of alpha-catenin and plakoglobin directly, by depleting the maternal mRNAs coding for each of them in developing Xenopus embryos. We find that depletion of maternal alpha-catenin causes the loss of intercellular adhesion at the blastula stage, similar to that reported previously for EP cadherin. Depletion of plakoglobin results in a partial loss of adhesion, and a loss of embryonic shape, but does not affect dorsal signalling.
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PMID:The roles of maternal alpha-catenin and plakoglobin in the early Xenopus embryo. 910 71

alpha-Catenin is a 102-kDa protein exhibiting homology to vincuin, and it forms complexes with cadherins or the tumor-suppressor gene product adenomatous polyposis coli through binding to beta-catenin or plakoglobin (gamma-catenin). The incorporation of alpha-catenin into the cadherin-catenin complexes is a prerequisite for expression of the cell-adhesive activity of cadherins. Using an in vitro assay system involving bacterially expressed proteins, we localized a region in alpha-catenin required for molecular interaction with beta-catenin and plakoglobin. Analysis of various truncated alpha-catenin molecules revealed that amino-terminal residues 48-163 are able to bind to beta-catenin and plakoglobin. Consistent with the observation that beta-catenin and plakoglobin bind to the same region of alpha-catenin, beta-catenin competed with the binding of plakoglobin to alpha-catenin and vice versa. Under the conditions used, beta-catenin bound to alpha-catenin with higher affinity than did plakoglobin. Scatchard analysis indicated that the affinity of the interaction between alpha-catenin and beta-catenin or that between alpha-catenin and plakoglobin was moderately strong (Kd = 3. 8 x 10(-8) and 7.7 x 10(-8), respectively). When transfected into L cells expressing E-cadherin, the amino-terminal region of alpha-catenin (from residue 1 to 226) formed complexes with beta-catenin supporting the in vitro binding experiment results.
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PMID:Identification of the domain of alpha-catenin involved in its association with beta-catenin and plakoglobin (gamma-catenin). 911 Sep 93

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. beta-catenin or plakoglobin is associated directly with the cadherin; alpha-catenin binds to beta-catenin/plakoglobin and serves to link the cadherin/catenin complex to the actin cytoskeleton. The domains on the cadherin and betacatenin/plakoglobin that are responsible for protein-protein interactions have been mapped. However, little is known about the molecular interactions between alpha-catenin and beta-catenin/plakoglobin or about the interactions between alpha-catenin and the cytoskeleton. In this study we have used the yeast two-hybrid system to map the domains on alpha-catenin that allow it to associate with beta-catenin/plakoglobin and with alpha-actinin. We also identify a region on alpha-actinin that is responsible for its interaction with alpha-catenin. The yeast two-hybrid data were confirmed with biochemical studies.
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PMID:Characterization of the interactions of alpha-catenin with alpha-actinin and beta-catenin/plakoglobin. 915 27

Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process.
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PMID:Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinomas of the head and neck and their nodal metastases. 916 40

E-cadherin and its associated cytoplasmic proteins alpha-, beta-, and gamma-catenin and p120 protein play a crucial role in the maintenance of normal tissue architecture. Perturbation in any of these molecules results in loss of intercellular adhesion and cell transformation. In this study, we have used immunohistochemistry to localize E-cadherin, alpha-, beta-, and gamma-catenin, and p120 in paraffin-embedded tissues from 60 patients with colonic polyps. Specimens consisted of 20 samples each from hyperplastic, inflammatory, and sporadic adenomatous polyps. Ten histologically normal colonic samples were also studied. Normal colonic epithelial cells showed strong E-cadherin/ catenin/p120 immunostaining at the cell-cell junction. In 65% (13/20) of adenomatous polyps, beta-catenin showed abnormal nuclear localization with increased expression and loss of membranous staining compared with the adjacent normal mucosa. In two cases (10%), gamma-catenin was seen in the nuclei. Heterogeneous p120 immunoreactivity was observed in four cases (20%), of which two also showed beta-catenin nuclear localization. Preserved membranous alpha-catenin staining was seen in all cases. E-cadherin was down-regulated in 6 of 20 (30%) adenomas with loss of cell surface staining in 3 cases. All hyperplastic and 40% (8/20) of inflammatory polyps showed weak E-cadherin expression on the surface epithelium. Similar changes in p120 expression were seen in all hyperplastic and 20% (4/20) of inflammatory polyps. There were no concomitant changes in alpha-, beta-, or gamma-catenin expression. These results indicate that changes in catenin expression and cellular localization occur early in dysplastic colonic lesions.
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PMID:Expression of E-cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120) in colorectal polyps. 917 91

During early heart development the expression pattern of N-cadherin, a calcium-dependent cell adhesion molecule, suggests its involvement in morphoregulation and the stabilization of cardiomyocyte differentiation. N-cadherin's adhesive activity is dependent upon its interaction with the intracellular catenins. An association with alpha-catenin and beta-catenin also is believed to be involved in cell signaling. This study details the expression patterns of alpha-catenin, beta-catenin, and gamma-catenin, during definition of the cardiac cell population as distinct compartments in the anterior regions of the chick embryo between stages 5 and 9. The restriction of N-cadherin/catenin localization at stage 5+ from a uniform pattern in vivo, to specific cell clusters that demarcate areas where mesoderm separation is initiated, suggests that the N-cadherin/catenin complex is involved in boundary formation and in the subsequent cell sorting. The latter two processes lead to the specification and formation of the somatic and cardiac splanchnic mesoderm. N-cadherin colocalized with alpha- and beta-catenin at the cell membrane before and during the time that its expression becomes restricted to the lateral mesoderm and continues cephalocaudad into stage 8. These proteins continue to colocalize in the myocardium of the tubular heart. Plakoglobin is not expressed in this region during stages 6-8, but is detected in the myocardium later at stage 13. The observed in vivo expression patterns of alpha-catenin, beta-catenin, and plakoglobin suggest that these proteins are directly linked with the developmental regulation of cell junctions, as cardiac cells become stably committed and phenotypically differentiated to eventually form a mature myocardium. The localization of N-CAM also was analyzed during these stages to determine whether the N-cadherin-catenin localization was unique or whether other cell adhesion molecules were expressed similarly. The results indicate that the unique pattern of N-cadherin expression is not shared with N-CAM. We also show that perturbation of N-cadherin using a function perturbing N-cadherin antibody (NCD-2) inhibits normal early heart development and myogenesis in a cephalocaudad, stage-dependent manner. We propose a model whereby myocardial cell compartmentalization also defines the endocardial population. The presence of beta-catenin suggests that a similar signaling pathway involving Wnt (wingless)-mediated events may function in myocardial cell compartmentalization during early vertebrate heart development, as in Drosophila contractile vessel development.
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PMID:N-cadherin-catenin interaction: necessary component of cardiac cell compartmentalization during early vertebrate heart development. 918 80

beta-catenin is a central component of the cadherin cell adhesion complex and plays an essential role in the Wingless/Wnt signaling pathway. In the current model of this pathway, the amount of beta-catenin (or its invertebrate homolog Armadillo) is tightly regulated and its steady-state level outside the cadherin-catenin complex is low in the absence of Wingless/Wnt signal. Here we show that the ubiquitin-dependent proteolysis system is involved in the regulation of beta-catenin turnover. beta-catenin, but not E-cadherin, p120(cas) or alpha-catenin, becomes stabilized when proteasome-mediated proteolysis is inhibited and this leads to the accumulation of multi-ubiquitinated forms of beta-catenin. Mutagenesis experiments demonstrate that substitution of the serine residues in the glycogen synthase kinase 3beta (GSK3beta) phosphorylation consensus motif of beta-catenin inhibits ubiquitination and results in stabilization of the protein. This motif in beta-catenin resembles a motif in IkappaB (inhibitor of NFkappaB) which is required for the phosphorylation-dependent degradation of IkappaB via the ubiquitin-proteasome pathway. We show that ubiquitination of beta-catenin is greatly reduced in Wnt-expressing cells, providing the first evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3beta in the regulation of beta-catenin.
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PMID:beta-catenin is a target for the ubiquitin-proteasome pathway. 923 89

The E-cadherin-catenin adhesion complex has been the subject of many structural and functional studies because of its importance in development, normal tissue function and carcinogenesis. It is well established that the cytoplasmic domain of E-cadherin binds either beta-catenin or plakoglobin, which both can assemble alpha-catenin into the complex. Recently we have identified an alpha-catenin binding site in beta-catenin and plakoglobin and postulated, based on sequence analysis, that these protein-protein interactions are mediated by a hydrophobic interaction mechanism. Here we have now identified the reciprocal complementary binding site in alpha-catenin which mediates its interaction with beta-catenin and plakoglobin. Using in vitro association assays with C-terminal truncations of alpha-catenin expressed as recombinant fusion proteins, we found that the N-terminal 146 amino acids are required for this interaction. We then identified a peptide of 27 amino acids within this sequence (amino acid positions 117-143) which is necessary and sufficient to bind beta-catenin or plakoglobin. As shown by mutational analysis, hydrophobic amino acids within this binding site are important for the interaction. The results described here, together with our previous work, give strong support for the idea that these proteins associate by hydrophobic interactions of two alpha-helices.
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PMID:A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin. 926 63

The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E-cadherin and alpha- and beta-catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico-pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E-cadherin, alpha-catenin, and beta-catenin was found in 74, 60, and 72 per cent, respectively. Expression of E-cadherin and alpha-catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta-catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E-cadherin and beta-catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E-cadherin, alpha-catenin and beta-catenin are related events. Furthermore, expression of at least E-cadherin and beta-catenin is significantly correlated with poor prognosis.
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PMID:Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis. 934 37

During the progression of many cancers, cell-cell adhesion molecules, e.g., E-cadherin (EC), may be down-regulated. In a number of carcinomas, EC has been described as an independent prognostic variable. We have studied the expression of adhesion molecules participating in cadherin-catenin complexes in renal cell carcinoma (RCC) specimens. Expression of EC, catenins and p120cas protein was examined in frozen tissue of 90 RCC specimens by immunohistochemistry, and these molecules were evaluated for their significance as prognostic markers. Staining was scored as normal (homogeneously positive at cell-cell borders) or abnormal (heterogeneous or absent). A significant correlation between poor survival and decreased expression of alpha-, beta- or gamma-catenin was observed, whereas no association between survival and EC or p120cas expression was seen. Cox's proportional hazard regression analysis showed that in patients with pT1-3N0M0 disease, reduced alpha-catenin expression correlated with poor survival, suggesting that alpha-catenin expression might be an independent prognostic indicator for patients of this group.
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PMID:Decreased expression of alpha-catenin is associated with poor prognosis of patients with localized renal cell carcinoma. 935 75


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