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

The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1 (PDZ)] protein erbin and delta-catenin, a component of the cadherin-catenin cell adhesion complex, are highly expressed in neurons and associate through PDZ-mediated interaction, but have incompletely characterized neuronal functions. We show that short hairpin RNA-mediated knockdown of erbin and knockdown or genetic ablation of delta-catenin severely impaired dendritic morphogenesis in hippocampal neurons. Simultaneous loss of erbin and delta-catenin does not enhance severity of this phenotype. The dendritic phenotype observed after erbin depletion is rescued by overexpression of delta-catenin and requires a domain in delta-catenin that has been shown to regulate dendritic branching. Knockdown of delta-catenin cannot be rescued by overexpression of erbin, indicating that erbin is upstream of delta-catenin. delta-Catenin-null neurons have no alterations in global levels of active Rac1/RhoA. Knockdown of erbin results in alterations in localization of delta-catenin. These results suggest a critical role for erbin in regulating dendritic morphogenesis by maintaining appropriate localization of delta-catenin.
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PMID:Erbin controls dendritic morphogenesis by regulating localization of delta-catenin. 1861 73

delta-Catenin is a member of the p120-catenin subfamily of armadillo proteins. Here, we describe distinctive features of delta-catenin localization and its association with E-cadherin in HEK293 epithelial cells. In HEK293 cells maintained in low cell densities, approximately 15% of cells overexpressing delta-catenin showed dendrite-like process formation, but there was no detectable change in RhoA activity. In addition, delta-catenin was localized mainly in the cytoplasm and was associated with p190RhoGEF. However, at high cell densities, delta-catenin localization was shifted to the plasma membrane. The association of delta-catenin with E-cadherin was strengthened, whereas its interaction with p190RhoGEF was weakened. In mouse embryonic fibroblast cell, ectopic expression of E-cadherin decreased the effect of delta-catenin on the reduction of RhoA activity as well as on dendrite-like process formation. These results suggest that delta-catenin is more dominantly bound to E-cadherin than to p190RhoGEF, and that delta-catenin's function is dependent on its cellular binding partner.
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PMID:E-Cadherin negatively modulates delta-catenin-induced morphological changes and RhoA activity reduction by competing with p190RhoGEF for delta-catenin. 1893 28

Different isoforms of p120-catenin (p120ctn), a member of the Armadillo gene family, are variably expressed in different tissues as a result of alternative splicing and the use of multiple translation initiation codons. When expressed in cancer cells, these isoforms may confer different properties with respect to cell adhesion and invasion. We have previously reported that the p120ctn isoforms 1 and 3 were the most highly expressed isoforms in normal lung tissues, and their expression level was reduced in lung tumor cells. To precisely define their biological roles, we transfected p120ctn isoforms 1A and 3A into the lung cancer cell lines A549 and NCI-H460. Enhanced expression of p120ctn isoform 1A not only upregulated E-cadherin and beta-catenin, but also downregulated the Rac1 activity, and as a result, inhibited the ability of cells to invade. In contrast, overexpression of p120ctn isoform 3A led to the inactivation of Cdc42 and the activation of RhoA, and had a smaller influence on invasion. However, we found that isoform 3A had a greater ability than isoform 1A in both inhibiting the cell cycle and reducing tumor cell proliferation. The present study revealed that p120ctn isoforms 1A and 3A differently regulated the adhesive, proliferative, and invasive properties of lung cancer cells through distinct mechanisms.
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PMID:P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells. 1915 Jun 13

p120-catenin, a member of the Armadillo gene family, has emerged as both a master regulator of cadherin stability and an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis. We have reported previously that abnormal expression of p120-catenin is associated with lymph node metastasis in lung squamous cell carcinomas (SCC) and adenocarcinomas. To investigate the role and possible mechanism of p120-catenin in lung cancer, we knocked down p120-catenin using small interfering RNA (siRNA). We found that ablation of p120-catenin reduced the levels of E-cadherin and beta-catenin proteins, as well as the mRNA of beta-catenin. Furthermore, p120-catenin depletion inactivated RhoA, but increased the activity of Cdc42 and Rac1, and promoted proliferation and the invasive ability of lung cancer cells both in vitro and in vivo. Our data reveal that p120-catenin gene knockdown enhances the metastasis of lung cancer cells, probably by either depressing cell-cell adhesion due to lower levels of E-cadherin and beta-catenin, or altering the activity of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.
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PMID:Ablation of p120-catenin enhances invasion and metastasis of human lung cancer cells. 1915 1

N-cadherin is a transmembrane adhesion receptor that contributes to neuronal development and synapse formation through homophilic interactions that provide structural-adhesive support to contacts between cell membranes. In addition, N-cadherin homotypic binding may initiate cell signaling that regulates neuronal physiology. In this study, we investigated signaling capabilities of N-cadherin that control voltage activated calcium influx. Using whole-cell voltage clamp recording of isolated inward calcium currents in freshly isolated chick ciliary ganglion neurons we show that the juxtamembrane region of N-cadherin cytoplasmic domain regulates high-threshold voltage activated calcium currents by interacting with p120-catenin and activating RhoA. This regulatory mechanism requires myosin interaction with actin. Furthermore, N-cadherin homophilic binding enhanced voltage activated calcium current amplitude in dissociated neurons that have already developed mature synaptic contacts in vivo. The increase in calcium current amplitude was not affected by brefeldin A suggesting that the effect is caused via direct channel modulation and not by increasing channel expression. In contrast, homotypic N-cadherin interaction failed to regulate calcium influx in freshly isolated immature neurons. However, RhoA inhibitors enhanced calcium current amplitude in these immature neurons, suggesting that the inhibitory effect of RhoA on calcium entry is regulated during neuronal development and synapse maturation. These results indicate that N-cadherin modulates voltage activated calcium entry by a mechanism that involves RhoA activity and its downstream effects on the cytoskeleton, and suggest that N-cadherin provides support for synaptic maturation and sustained synaptic activity by facilitating voltage activated calcium influx.
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PMID:N-cadherin modulates voltage activated calcium influx via RhoA, p120-catenin, and myosin-actin interaction. 1916 91

Studies on a variety of cell lines have shown that p120-catenin can directly regulate the stability of E-cadherin complexes and control the activity of small GTPases to influence cell adhesion. Despite this data, clinical studies of human solid tumors have not been reported to investigate these protein interactions. To explore the correlation between p120-catenin, E-cadherin, and small GTPases in human lung cancer, we examined the expression patterns of p120-catenin, E-cadherin, RhoA, Cdc42, and Rac1, and their prognostic significance in 138 patients with non-small cell lung cancer (NSCLC). While normal bronchial epithelium showed strong membrane expression of p120-catenin and E-cadherin, lung cancer tissues had reduced membrane expression and ectopic cytoplasmic expression of p120-catenin and E-cadherin. Expression of RhoA, Cdc42, and Rac1 was also found to be higher in tumor tissue than in normal lung tissue. A correlation between abnormal p120-catenin, E-cadherin expression, and overexpression of specific small GTPases was also associated with poor differentiation, high TNM stage, and lymph node metastasis in NSCLC patients. We also used an in vitro model to evaluate their expression, and to determine whether protein expression correlated with the invasive capacity of lung cancer cell lines. Consistent with our in vivo data, abnormal expression of p120-catenin and E-cadherin with overexpression of specific small GTPases were significantly associated with the high metastatic capacity of BE1 cells. Based on our results, we conclude that abnormal p120-catenin expression correlates with abnormal E-cadherin expression and specific small GTPase overexpression, which contribute to the malignancy-related to NSCLC.
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PMID:Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer. 1916 67

p120-catenin regulates epithelial cadherin stability and has been suggested to function as a tumor suppressor. In this study, we used anchorage-independent growth (AIG), a classical in vitro tumorigenicity assay, to examine the role of p120 in a different context, namely oncogene-mediated tumorigenesis. Surprisingly, p120 ablation by short hairpin RNA completely blocked AIG induced by both Rac1 and Src. This role for p120 was traced to its activity in suppression of the RhoA-ROCK pathway, which appears to be essential for AIG. Remarkably, the AIG block associated with p120 ablation was completely reversed by inhibition of the downstream RhoA effector ROCK. Harvey-Ras (H-Ras)-induced AIG was also dependent on suppression of the ROCK cascade but was p120 independent because its action on the pathway occurred downstream of p120. The data suggest that p120 modulates oncogenic signaling pathways important for AIG. Although H-Ras bypasses p120, a unifying theme for all three oncogenes is the requirement to suppress ROCK, which may act as a gatekeeper for the transition to anchorage independence.
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PMID:An essential role for p120-catenin in Src- and Rac1-mediated anchorage-independent cell growth. 1918 96

p120-catenin is a cytoplasmic binding partner of cadherins and functions as a set point for cadherin expression by preventing cadherin endocytosis, and degradation. p120 is known to regulate cell motility and invasiveness by inhibiting RhoA activity. However, the relationship between these functions of p120 is not understood. Here, we provide evidence that p120 functions as part of a plasma membrane retention mechanism for VE-cadherin by preventing the recruitment of VE-cadherin into membrane domains enriched in components of the endocytic machinery, including clathrin and the adaptor complex AP-2. The mechanism by which p120 regulates VE-cadherin entry into endocytic compartments is dependent on p120's interaction with the cadherin juxtamembrane domain, but occurs independently of p120's prevention of Rho GTPase activity. These findings clarify the mechanism for p120's function in stabilizing VE-cadherin at the plasma membrane and demonstrate a novel role for p120 in modulating the availability of cadherins for entry into a clathrin-dependent endocytic pathway.
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PMID:p120-catenin inhibits VE-cadherin internalization through a Rho-independent mechanism. 1921 43

p120 catenin is a major regulator of cadherin stability at cell-cell contacts and a modulator of Rho GTPase activities. In C2C12 myoblasts, N-cadherin is stabilized at cell contacts through its association with cholesterol-rich membrane domains or lipid rafts (LR) and acts as an adhesion-activated receptor that activates RhoA, an event required for myogenesis induction. Here, we report that association of p120 catenin with N-cadherin at cell contacts occurs specifically in LR. We demonstrate that interaction of p120 catenin with N-cadherin is required for N-cadherin association with LR and for its stabilization at cell contacts. LR disruption inhibits myogenesis induction and N-cadherin-dependent RhoA activation as does the perturbation of the N-cadherin-p120 catenin complex after p120 catenin knockdown. Finally, we observe an N-cadherin-dependent accumulation of RhoA at phosphatidylinositol 4,5-bisphosphate-enriched cell contacts which is lost after LR disruption. Thus, a functional N-cadherin-catenin complex occurs in cholesterol-rich membrane microdomains which allows the recruitment of RhoA and the regulation of its activity during myogenesis induction.
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PMID:N-cadherin/p120 catenin association at cell-cell contacts occurs in cholesterol-rich membrane domains and is required for RhoA activation and myogenesis. 1954 17

Catenins of the p120 subclass display an array of intracellular localizations and functions. Although the genetic knockout of mouse delta-catenin results in mild cognitive dysfunction, we found severe effects of its depletion in Xenopus. delta-catenin in Xenopus is transcribed as a full-length mRNA, or as three (or more) alternatively spliced isoforms designated A, B and C. Further structural and functional complexity is suggested by three predicted and alternative translation initiation sites. Transcript analysis suggests that each splice isoform is expressed during embryogenesis, with the B and C transcript levels varying according to developmental stage. Unlike the primarily neural expression of delta-catenin reported in mammals, delta-catenin is detectable in most adult Xenopus tissues, although it is enriched in neural structures. delta-catenin associates with classical cadherins, with crude embryo fractionations further revealing non-plasma-membrane pools that might be involved in cytoplasmic and/or nuclear functions. Depletion of delta-catenin caused gastrulation defects, phenotypes that were further enhanced by co-depletion of the related p120-catenin. Depletion was significantly rescued by titrated p120-catenin expression, suggesting that these catenins have shared roles. Biochemical assays indicated that delta-catenin depletion results in reduced cadherin levels and cell adhesion, as well as perturbation of RhoA and Rac1. Titrated doses of C-cadherin, dominant-negative RhoA or constitutively active Rac1 significantly rescued delta-catenin depletion. Collectively, our experiments indicate that delta-catenin has an essential role in amphibian development, and has functional links to cadherins and Rho-family GTPases.
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PMID:Xenopus delta-catenin is essential in early embryogenesis and is functionally linked to cadherins and small GTPases. 1984 87


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