Disease relevance of CTNND1

• p120-catenin expression in human colorectal cancer [1].
• Ischemia promotes calpain-mediated degradation of p120-catenin in SH-SY5Y cells [2].
• In this study, we have evaluated the expression of alpha-catenin but also of the other catenins (beta-, gamma- and p120-catenin) and E-cadherin in invasive breast cancer and statistically analysed these expressions with known clinicopathological parameters, c-erbB-2 oncoprotein expression and patient survival [3].
• Inducible expression of p120Cas1B isoform corroborates the role for p120-catenin as a positive regulator of E-cadherin function in intestinal cancer cells [4].
• Eight adult cases with myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related (pauci-immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti-pan cadherin, p120 catenin, and beta-catenin antibodies [5].
• Membranous p120 is maintained in invasive squamous cell carcinomas in tumours suggesting that p120 may be important for the collective invasion of tumours cells in vivo [6].
• The data indicate that the increased expression of p120 isoform 1 during tumor progression contributes to the invasive phenotype of cadherin-deficient carcinomas and that the N-terminal domain of p120 is a valid therapeutic target [7].

High impact information on CTNND1

• Although p120-catenin regulates adherens junction (AJ) stability in cultured cells, genetic studies in lower eukaryotes have not revealed a role for this protein in vivo [8].
• A series of recent studies indicate that a core function of p120-catenin in mammalian cells is to regulate cadherin turnover by modulating the entry of cadherins into degradative endocytic pathways [9].
• Collectively, the findings suggest exciting new roles for p120-catenin at the interface between cadherins and membrane trafficking machinery, and imply novel mechanisms by which p120-catenin may regulate cell adhesion and migration in the context of development and cancer [9].
• As Kaiso associates with p120 catenin, Kaiso may link events at the cell surface with DNA methylation-dependent gene silencing [10].
• A cloned subline of the human monocytic leukemia cell line, THP-1, was induced to produce high levels of cytotoxic activity following an 18-hour phorbol myristate acetate (CAS: 16561-29-8) stimulation in vitro [11].

Chemical compound and disease context of CTNND1

• The safety of the antioxidant alpha-lipoic acid (racemic form) (ALA), also called thioctic acid (CAS RN 1077-28-7) was assessed in acute and subchronic toxicity studies as well as in in vitro and in vivo mutagenicity/genotoxicity studies [12].
• In the present communication, the long-term efficacy and safety of nipradilol were investigated and the efficacy, safety and utility of topical nipradilol and timolol (CAS 91524-16-2) were compared in patients with primary open-angle glaucoma or ocular hypertension [13].
• The pharmacodynamic pattern of low molecular weight dermatan sulphate (CAS 24967-94-0, Desmin-LMWDS) was studied in patients presenting chronic renal insufficiency [14].
• The effects of benidipine hydrochloride (benidipine, CAS 91559-74-5), a dihydropyridine calcium antagonist, on the 24-h ambulatory blood pressure were studied by a double-blind test against placebo in 8 patients with essential hypertension [15].
• Dose dependent percent inhibition of granuloma formation, exudate volume, total leukocyte count was observed in 4e (25, 50 and 100 mg/kg) and celecoxib (CAS 169590-42-5; 5 mg/kg) treated groups in the cotton pellet granuloma and granuloma pouch technique, respectively, in rats [16].

Biological context of CTNND1

• Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin [17].
• VE-cadherin can interact with p120 catenin (p120(ctn)) to mediate cell locomotion and proliferation [18].
• Laminar shear stress differentially modulates gene expression of p120 catenin, Kaiso transcription factor, and vascular endothelial cadherin in human coronary artery endothelial cells [18].
• p120-Catenin regulates clathrin-dependent endocytosis of VE-cadherin [19].
• Finally, our results for the first time demonstrate that the interaction of VE-cadherin with p120 catenin plays an important role in cellular growth, suggesting that the binding of p120 catenin to cadherins may regulate cell proliferation [20].

Anatomical context of CTNND1

• Cellular levels of p120 catenin function as a set point for cadherin expression levels in microvascular endothelial cells [21].
• TNF-alpha also increased tyrosine phosphorylation of EC proteins, and several substrates were identified as the zonula adherens proteins vascular endothelial (VE)-cadherin, and beta-catenin, gamma-catenin, and p120 catenin (p120(ctn)) [22].
• p120 catenin associates with kinesin and facilitates the transport of cadherin-catenin complexes to intercellular junctions [23].
• p120 catenin regulates the actin cytoskeleton via Rho family GTPases [24].
• Cell fractionation demonstrated a predominant decrease in the particulate (membrane-bound) pool of p120 catenin with little effect on the soluble pool, resulting in a large redistribution from the plasma membrane to the cytosol [25].

Associations of CTNND1 with chemical compounds

• Yes tyrosine kinase also binds to p120 catenin but only upon activation, and stimulates Fer and Fyn tyrosine kinases [26].
• Immunoprecipitation of transgenic brain extracts with anti-myc antibodies demonstrates an interaction with cadherins, beta-catenin, and p120 catenin, as well as with the associated proteins calcium calmodulin-dependent serine kinase and Velis, but not with alpha-catenin [27].
• Using co-immunoprecipitation and pull-down assays we show here that nephrin forms a multiprotein complex with cadherins and p120 catenin and with three scaffolding proteins, ZO-1, CD2AP, and CASK, in kidney glomeruli and when expressed in Madin-Darby canine kidney cells [28].
• Phosphorylated "optimal Src substrate" AEEEIpYGEFEA (where pY is phosphotyrosine) and a phosphopeptide corresponding to a recently identified Src phosphorylation site in p120 catenin, DDLDpY(296)GMMSD, were excellent SHP-1 substrates [29].
• Reexpression of p120 catenin inhibited constitutive (transferrin receptor) and regulated mannose 6-phosphate receptor and GLUT4 trafficking to the plasma membrane [25].

Physical interactions of CTNND1

• p120-catenin stabilizes epithelial cadherin (E-cadherin) in SW48 cells, but the mechanism has not been established [30].
• Assembly of the N-cadherin complex during synapse formation involves uncoupling of p120-catenin and association with presenilin 1 [31].

Enzymatic interactions of CTNND1

• The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin [32].

Regulatory relationships of CTNND1

• VE-cadherin expression levels are regulated by p120 catenin, which prevents lysosomal degradation of cadherins by unknown mechanisms [19].
• p120-catenin (p120(ctn)) interacts with the cytoplasmic tail of cadherins and is thought to regulate cadherin clustering during formation of adherens junctions [33].
• We show that coexpression of Glis2 and Src induces nuclear translocation of p120 [34].

Other interactions of CTNND1

• A core function for p120-catenin in cadherin turnover [30].
• Both type I and type II cadherins are composed of five extracellular repeat domains with conserved calcium-binding motifs, a single pass transmembrane domain, and a highly conserved cytoplasmic domain that interacts with beta-catenin and p120 catenin [35].
• More recently, attention has been directed towards p120-catenin, which in conjunction with the p120-catenin sub-family members ARVCF- and delta-catenins, are the subjects of this review [36].
• During 3T3L1 adipogenesis there is a marked reduction in beta-catenin and N-cadherin expression with a relatively small decrease in p120 catenin protein levels [25].
• Although originally identified as a Src substrate, p120-catenin (p120) is now known to regulate cell-cell adhesion through its interaction with the cytoplasmic tail of classical and type II cadherins [37].

Analytical, diagnostic and therapeutic context of CTNND1

• Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms [38].
• Association of p120-catenin to the cytoskeleton was also determined in 5 tumors by detergent extraction and Western blot; this analysis shows that lack of reactivity in the membrane was accompanied by absence of p120-catenin in the cytoskeleton-associated fraction [1].
• Nineteen randomized patients, treated with isoniazid (INH, CAS 54-85-3) for tuberculosis chemoprophylaxis or isoniazid plus rifampicin (RMP, CAS 13292-46-1) combination for tuberculosis therapy, were studied in order to explore the effects of these drugs on fibrinogen and antithrombin III blood levels [39].
• We have assessed the bone cuts achieved at surgery as compared to the planned cuts produced during computer assisted surgery (CAS) using a CT-free navigation system [40].
• Using the CAS system, the surgeon is continuously apprised of the precise position of the surgical instrument vis-a-vis all relevant anatomical structures [41].

References