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)

As transmembrane, Ca2+-dependent cell-cell adhesion molecules, cadherins play a central role in tissue morphogenesis and homeostasis. Stable adhesion is dependent on interactions of the cytoplasmic domain of the cadherins with a group of intracellular proteins, the catenins. In the present study, we have detected the expression of alpha-, beta-, and gamma-catenins in human osteoblasts, which assemble with cadherins to form two distinct complexes containing cadherin and alpha-catenin, with either beta- or gamma-catenin. In osteoblasts undergoing apoptosis, proteolytic cleavage of N-cadherin and beta- and gamma- catenins but not alpha-catenin was associated with the activation of caspase-3 and prevented by the caspase inhibitor Z-VAD-fmk. The pattern of cadherin/catenin cleavage detected in apoptotic osteoblasts was reproduced in vitro by recombinant caspase-3. The presence of a 90-kDa extracellular domain fragment of N-cadherin in conditioned medium from apoptotic cells indicates that additional extracellular or membrane-associated proteases also are activated. Disruption of N-cadherin-mediated cell-cell adhesion with function-blocking antibodies induced osteoblast apoptosis, activation of caspases, and cleavage of beta-catenin. These findings provide compelling evidence that N-cadherin-mediated cell-cell adhesion promotes osteoblast survival and suggest that the underlying mechanism may involve activation of beta-catenin signaling.
 ...
PMID:Caspase-dependent cleavage of cadherins and catenins during osteoblast apoptosis. 1127 64

Previous work has shown that chemically induced oxidative stress disrupts the protein interactions of the E-cadherin/beta-catenin/alpha-catenin complex in precision-cut mouse liver slices (Parrish et al., 1999, Toxicol. Sci. 51, 80-86). Although these data suggest a role for oxidative stress in disruption of hepatic cadherin/catenin complexes, multiple complexes are co-expressed in the liver. Both E- and N- cadherin are co-expressed in hepatocytes, as well as beta-catenin and gamma-catenin; thus four distinct complexes mediate cell-cell adhesion in the liver: E-cadherin/beta-catenin/alpha-catenin, E-cadherin/gamma-catenin/alpha-catenin, N-cadherin/beta-catenin/alpha-catenin, and N-cadherin/gamma-catenin/alpha-catenin. Taking advantage of the retention of normal organ architecture and cellular heterogeneity offered by precision-cut mouse liver slices, the current study was designed to examine the impact of chemically induced oxidative stress on cadherin/catenin complexes. Precision-cut mouse liver slices were challenged with diamide (25-250 microM; 6 h) or tert-butylhydroperoxide (5-50 microM; 6 h). A polyclonal antibody against beta- or gamma-catenin was used to immunoprecipitate proteins prior to Western-blot analysis with monoclonal antibodies to E- or N-cadherin. Although a decrease in E-cadherin:beta-catenin co-immunoprecipitation was seen, interactions between beta-catenin and N-cadherin were not disrupted by chemical challenge. In addition, no effect on protein interactions of gamma-catenin with either cadherin was observed. Indirect immunofluorescence was used to co-localize catenins and cadherins following chemical challenge. Consistent with the biochemical observations, a heterogeneous reduction in co-localization of E-cadherin and beta-catenin was seen in precision-cut liver slices, but not other cadherin/catenin complexes. Taken together, these data suggest that oxidative stress selectively disrupts E-cadherin/beta-catenin complexes in the liver. This response is dictated, in part, by the protein composition of the cell-adhesion complex.
 ...
PMID:Selective disruption of cadherin/catenin complexes by oxidative stress in precision-cut mouse liver slices. 1135 48

The cadherins play key roles in the formation and organization of the mammalian placenta by mediating cellular interactions and the terminal differentiation of trophoblastic cells. Although cadherin function is regulated by the cytoplasmic proteins, known as the catenins, the identity and expression pattern(s) of the catenins present in the trophoblastic cells of the human placenta have not been characterized. In these studies, we have determined that alpha-, beta-, gamma-catenin, and p120(ctn) expression levels are high in villous cytotrophoblasts isolated from the human term placenta but decline as these cells undergo aggregation and fusion to form syncytium with time in culture. In contrast, the expression levels of these four catenin subtypes remained constant in non-fusing JEG-3 choriocarcinoma cells at all of the time points examined in these studies. alpha-, beta-, gamma-catenin, and p120(ctn) expression was further immunolocalized to the mononucleate cells present in these two trophoblastic cell cultures. Similarly, intense immunostaining for all four catenins was detected in the mononucleate villous cytotrophoblasts of the human first trimester placenta. Collectively, these observations demonstrate that the expression levels of alpha-, beta-, gamma-catenin, and p120(ctn) are tightly regulated during the formation of multinucleated syncytium in vitro and in vivo.
 ...
PMID:alpha-, beta-, gamma-catenin, and p120(CTN) expression during the terminal differentiation and fusion of human mononucleate cytotrophoblasts in vitro and in vivo. 1138 51

The activation of the adenomatous polyposis coli (APC)/beta-catenin/T-cell factor (Tcf) pathway due to beta-catenin gene mutation has been recently implicated in the development of some endometrial carcinomas. beta- and gamma-catenin are structurally and functionally related molecules that participate in cell adhesion and signal transduction. Nuclear accumulation of beta- and gamma-catenin have been related to the activation of the APC/beta-catenin/Tcf pathway. In this study, we investigate the immunohistochemical expression pattern (nuclear vs membranous) of beta- and gamma-catenin in 40 endometrial carcinomas and their correlation with clinicopathological features and microsatellite instability (MI) status. MI was detected at three or more loci in 12 tumors: 11 were endometrioid and one was non-endometrioid. Nuclear catenin expression was found in 13 carcinomas: ten carcinomas had nuclear beta-catenin expression and three carcinomas had nuclear gamma-catenin expression. The nuclear catenin expression pattern significantly correlated with the histological type, International Federation of Gynecology and Obstetrics (FIGO) grade, and the presence of a second neoplasm. Nuclear catenin expression was always observed in low-grade endometrioid carcinomas; it was also more frequently associated with a second carcinoma. No correlation was observed between the catenin expression pattern and the level of myometrial infiltration, stage, associated endometrial hyperplasia, the existence of a source of estrogenic stimulation, and MI. However, four of 13 endometrioid carcinomas in this series had both catenin nuclear expression and MI. These data suggest that at least two different neoplastic pathways can lead to endometrial carcinomas with an endometrioid phenotype. In one, MI would be a key event, while in the other, the APC/beta-catenin/Tcf signaling pathways could be activated. Probably, in some cases, both pathways could simultaneously occur.
 ...
PMID:Beta- and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability. 1140 74

Dysfunction of E-cadherin and catenin has been linked to invasiveness and differentiation of tumors. This study aimed to characterize the expression of cadherins and catenins in early gastric carcinoma and their relationship to clinicopathologic characteristics and Helicobacter pylori infection. E-cadherin and alpha-, beta- and gamma-catenins were strongly expressed in normal epithelium but abnormal immunoreactivity of at least one of these four proteins was noted in 48 (90.6%) of 53 early gastric carcinomas. Only 5 cases with intestinal-type tumors had intact expression of E-cadherin and alpha-, beta-, and gamma-catenins. Abnormal immunoreactivity in the tumor tissue was observed in 18 patients (34.0%) for E-cadherin, in 35 (66.0%) for alpha-catenin, in 20 (37.7%) for beta-catenin, and in 37 (69.8%) for gamma-catenin. In diffuse-type tumors, abnormal expression of E-cadherin (60.9 vs. 13.3%, p < 0.0005), alpha-catenin (82.6 vs. 53.3%, p < 0.05) and gamma-catenin (91.3 vs. 53.3%, p < 0.005) was more frequent than in the intestinal type. Ten tumors with lymph node metastasis showed a relatively higher frequency of abnormal expression of E-cadherin (70 vs. 25.6%, p < 0.05) but a lower frequency of abnormal expression of beta-catenin (10 vs. 44.1%, p = 0.07) than those without metastasis. No significant association was found between cadherin/catenin expression and the depth of invasion or the H. pylori status. It was concluded that abnormal expression of E-cadherin and the catenin-mediated cell-cell adhesion system occurs frequently in early gastric carcinogenesis and may play an important role in the genesis of histologic differentiation and in the mode of metastasis of early gastric carcinomas.
 ...
PMID:Immunohistochemical evaluation of cadherin and catenin expression in early gastric carcinomas: correlation with clinicopathologic characteristics and Helicobacter pylori infection. 1140 2

The cadherin/catenin complex regulates cellular adhesion and motility and is believed to function as an invasion suppressor system. Several studies have identified alterations in the expression profiles of those molecules in different histotypes of thyroid carcinoma. The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare, highly invasive variant of PTC in which an impairment of cell-cell adhesion may play a major role. In an attempt to progress in the understanding of the clinicopathological features of DSV, this study examined eight cases of DSV, 18 cases of classical PTC and a control group of normal thyroid by immunohistochemistry (E-, P- and N-cadherins and beta-, gamma- and alpha-catenins). The E-cadherin gene was also studied by polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) and methylation-specific PCR (MSP). In contrast to classical PTC, which showed heterogeneous loss of E-cadherin expression, in almost every case of DSV a pronounced reduction was observed in its membranous expression, accompanied by a relocation to the cytoplasm. Inactivation of the E-cadherin/catenin complex appears to occur in DSV via two different pathways: E-cadherin alteration either through mutation (one out of the eight cases) or through methylation of the E-cadherin gene promoter (three out of five cases); and beta- and/or gamma-catenin alterations (three of the eight cases). Methylation of the E-cadherin gene promoter, abnormalities of E-cadherin expression and alterations of gamma-catenin were also detected in classical PTC. In DSV, as in classical PTC, there is neo-expression of P-cadherin in areas of squamous metaplasia and no N-cadherin expression. In conclusion, abnormalities of the E-cadherin/catenin complex appear to be more pronounced in DSV than in classical PTC. It remains to be shown whether or not such differences are associated with the more aggressive behaviour of DSV compared with classical PTC.
 ...
PMID:Abnormalities of the E-cadherin/catenin adhesion complex in classical papillary thyroid carcinoma and in its diffuse sclerosing variant. 1143 69

Alpha-catenin, an intracellular protein, associates with the COOH-terminal region of cadherin cell adhesion molecules through interactions with either beta-catenin or gamma-catenin (plakoglobin). The full activity of cadherins requires a linkage to the actin cytoskeleton mediated by catenins. We transfected alpha-catenin-deficient colon carcinoma cells with a series of alpha-catenin constructs to determine that alpha-catenin expression increases the resistance to apoptosis induced by sphingosine. Two groups of constructs, containing deletions in either the middle segment of the molecule or the COOH terminus, induced morphological changes, cell compaction, and decreases in cell death. In alpha-catenin-expressing cells, inhibition of cadherin cell adhesion by treatment with anti-E-cadherin antibodies did not decrease the cells viability. alpha-Catenin expression partially suppressed the downregulation of Bcl-xL and the activation of caspase 3. Expression of p27kip1 protein, an inhibitor of cyclin-dependent kinases, was increased by alpha-catenin expression in low density cell cultures. The increased levels of p27kip1 correlated with both increased resistance to cell death and morphological changes in transfectants containing deletion mutants. Transfection-mediated upregulation of p27kip1 decreases sphingosine-induced cell death in alpha-catenin-deficient cells. We postulate that alpha-catenin mediates transduction of signals from the cadherin-catenin complex to regulate the apoptotic cascade via p27kip1.
 ...
PMID:Expression of alpha-catenin in alpha-catenin-deficient cells increases resistance to sphingosine-induced apoptosis. 1148 17

The cadherin-catenin system mediates Ca(2+)-dependent cell-cell adhesion, and genetic alterations in these molecules play a significant role in multistage carcinogenesis. Mutations in the beta-catenin gene, mostly affecting exon 3, have been detected in malignant cell lines and in primary tumors. Immunohistochemical abnormalities in alpha-, beta-, and gamma-catenin have been reported in malignant and benign tumors, and nuclear localization of beta-catenin has been associated with mutations in exon 3 of this gene. Mutational analysis of exon 3 of the beta-catenin gene was undertaken by polymerase chain reaction (PCR) and sequencing using genomic DNA extracted from frozen tissues, including 4 normal pituitaries, 22 pituitary adenomas, and one pituitary carcinoma. Frozen sections from these cases were used for immunohistochemical detection of beta-catenin. We also analyzed immunohistochemical expression of alpha-, beta-, and gamma-catenin by paraffin sections from 154 pituitary tumors, including 148 adenomas and 6 carcinomas. Genomic DNA was extracted from paraffin sections of 2 gonadotroph tumors showing nuclear staining for beta-catenin and was used for PCR and sequencing of exon 3 of the beta-catenin gene. No mutations in exon 3 of the beta-catenin gene were found in any of the 23 cases analyzed by PCR and sequencing. In addition, the 2 cases studied by paraffin section immunohistochemistry, with nuclear staining for beta-catenin, were negative for mutations in this exon. Normal pituitary expressed all three catenin proteins. Immunostaining usually showed a membranous pattern of reactivity and was generally stronger in normal pituitary than in the adjacent adenomas. Stains for alpha-catenin were positive in fewer tumors than for beta-catenin. The lowest frequency immunopositive tumors and the weakest immunostaining was for gamma-catenin. All medically treated prolactinomas were negative for gamma-catenin, whereas treated growth hormone adenomas were less often positive for both alpha- and gamma-catenin than for untreated tumors. The percentage of positive cases for beta-catenin was the same in these two groups. Most pituitary carcinomas were negative for both alpha- and gamma-catenin but were beta-catenin positive. These results indicate that (i) mutations in exon 3 of the beta-catenin gene are uncommon in pituitary tumors, and (ii) expression of alpha-, beta-, and gamma-catenin is decreased in pituitary adenomas compared to normal pituitary tissues.
 ...
PMID:Analysis of beta-catenin mutations and alpha-, beta-, and gamma-catenin expression in normal and neoplastic human pituitary tissues. 1157 78

Cellular adhesion is regulated by members of the cadherin family of adhesion receptors and their cytoplasmic adaptor proteins, the catenins. Adhesion complexes are regulated by recycling from the plasma membrane and proteolysis during apoptosis. We report that in MCF-7, MDA-MB-468 and MDCK cells, induction of apoptosis by agents that cause endoplasmic reticulum (ER) stress results in O-glycosylation of both beta-catenin and the E-cadherin cytoplasmic domain. O-glycosylation of newly synthesized E-cadherin blocks cell surface transport, resulting in reduced intercellular adhesion. O-glycosylated E-cadherin still binds to beta- and gamma-catenin, but not to p120-catenin. Although O-glycosylation can be inhibited with caspase inhibitors, cleavage of caspases associated with the ER or Golgi complex does not correlate with E-cadherin O-glycosylation. However, agents that induce apoptosis via mitochondria do not lead to E-cadherin O-glycosylation, and decrease adhesion more slowly. In MCF-7 cells, this is due to degradation of E-cadherin concomitant with cleavage of caspase-7 and its substrate poly(ADP-ribose) polymerase. We conclude that cytoplasmic O-glycosylation is a novel, rapid mechanism for regulating cell surface transport exploited to down-regulate adhesion in some but not all apoptosis pathways.
 ...
PMID:Cytoplasmic O-glycosylation prevents cell surface transport of E-cadherin during apoptosis. 1168 40

The E-cadherin/catenin complex plays a major role in epithelial cell-cell adhesion. Immunohistochemical studies have highlighted perturbation in the expression and distribution of E-cadherin and catenins in sporadic colorectal neoplasms. In this study, we compared the expression of E-cadherin and catenins (alpha-, beta-, and gamma-catenin) in 30 sporadic colorectal carcinomas with that in the adjacent nonneoplastic mucosa and assessed whether any perturbation in the level of expression occurred at the messenger RNA (mRNA) or protein level. We also compared the expression of E-cadherin and catenins in 13 lymph node deposits and the primary tumors. Immunohistochemistry was used to study the level of expression and cellular distribution of E-cadherin and catenins. Levels of mRNA were studied by in situ hybridization. E-cadherin and catenin immunoreactivity was increased with cytoplasmic accumulation in more than 85% of the neoplasms. There were marked increases in the levels of mRNA in the carcinomas compared with the nonneoplastic mucosa. Nuclear localization of beta-catenin was higher at the invasive margin of some tumors, but expression of E-cadherin and catenin transcripts in the lymph node deposits showed no consistent relationship to that in the primary tumors.
 ...
PMID:The expression of E-cadherin and catenins in sporadic colorectal carcinoma. 1172 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>