Disease relevance of CTNNA1

• We show here that one allele of the alphaE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18 [1].
• The cadherin-associated proteins, alpha-catenin and beta-catenin, were present in both mesotheliomas and adenocarcinomas [2].
• Using phage display, we identified Na(+)/H(+) exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-associated protein, beta-catenin [3].
• These data suggest that the E-cadherin-alpha E-catenin complex is well preserved in human schwannoma cells, which is compatible with its benign behavior, and these molecules might be used as additional cell markers of Schwann cell-derived tumors [4].

High impact information on CTNNA1

• Recent results address molecular explanations for observed cadherin behavior, point to signals that regulate adhesion by modulating elements of the cadherin-associated complex, challenge the belief that different cadherins generally cannot cross-adhere, and highlight instructive roles for cadherins in cell signaling and differentiation [5].
• alphaE-catenin, a cadherin-associated protein, is required for tight junction (TJ) organization, but its role is poorly understood [6].
• Cadherin-associated gelsolin severing activity was required for localized actin assembly as determined by rhodamine actin monomer incorporation onto actin barbed ends at intercellular adhesion sites [7].
• In addition, we have determined that the cadherin-associated protein, known as beta-catenin, is expressed in normal peritoneum, ovarian tumors and malignant cell effusions obtained from women with Stage I or Stage II cancer [8].
• We have identified and characterized a cDNA designated CTNNBL1 (catenin (cadherin-associated protein), beta-like 1) coding for a protein of 563 amino acids having predicted structural homology to beta-catenin and other armadillo (arm) family proteins [9].

Biological context of CTNNA1

• Assignment of the human alpha-catenin gene (CTNNA1) to chromosome 5q21-q22 [10].
• Allelic imbalance occurs at two distinct regions of which one includes the CTNNA1 gene [11].
• Loss of the CTNNA1 gene did not appear to be involved in down-regulation of alpha-catenin in ovarian tumors, since allelic imbalance with a variety of markers, including CTNNA1 associated marker D5S476, was found in tumor samples independently of alpha-catenin expression [11].
• The transcript of CTNNA1 is 3.4 kb long and consists of 16 coding exons encoding 906 amino acids and at least one 5' noncoding exon [12].
• Mutations of the alphaE-catenin gene, CTNNA1, were described in several human cancer cell lines and were found to result in aberrant cell adhesion [13].

Anatomical context of CTNNA1

• To test the efficiency of the panel PCR amplification of DNA from the monochromosomal somatic cell hybrid panel was used in combination with human specific oligonucleotide primers to assign alpha-catenin (CTNNA1) and p21/WAF1 to chromosomes 5 and 6 respectively [14].
• Furthermore, phosphorylation of the integrin-regulated focal adhesion kinase (FAK) on Src-specific sites is required for Src-induced de-regulation of E-cadherin, demonstrating interdependence between integrin-induced signals and cadherin-associated adhesion changes induced by Src [15].
• The gene designated as CTNNAL1 (catenin (cadherin-associated protein), alpha-like 1) was found to be ubiquitously expressed in many tissues including pancreas, heart, and skeletal muscle [16].
• Cadherins and cadherin-associated molecules have been identified in testes and germinal cells, as well as ejaculated spermatozoa [17].
• alpha-E-catenin inactivation disrupts the cardiomyocyte adherens junction, resulting in cardiomyopathy and susceptibility to wall rupture [18].

Associations of CTNNA1 with chemical compounds

• Furthermore, Src-induced deregulation of E-cadherin requires integrin signalling, demonstrating a complex interdependence between integrin- and cadherin-associated adhesion changes induced by Src [19].
• Analysis of putative second messengers shows that treatment of the embryos with anti-cadherin Fabs leads to a decreased tyrosine phosphorylation of the two cadherins and of two cadherin-associated proteins and to a doubling of the intracellular concentration of cAMP [20].

Physical interactions of CTNNA1

• Immunoprecipitation using anti-E-cadherin antibody resulted in alpha E-catenin forming a complex with E-cadherin [4].

Regulatory relationships of CTNNA1

• Further, angio-associated protein, alpha E-catenin and atrial brain natriuretic peptide receptor were downregulated whereas TFPI 2 was strongly upregulated in invasive haSMCs [21].

Other interactions of CTNNA1

• The nuclear localization of E-cadherin did not correlate with cadherin-associated protein beta-catenin nuclear expression [22].
• Structure, expression and chromosome assignment of the human catenin (cadherin-associated protein) alpha 1 gene (CTNNA1) [12].
• A pseudogene (CTNNAP1) for the human alpha E-catenin gene was isolated from a human genomic phage library [23].
• A previous study issued from our laboratory demonstrated that alpha N-catenin is localized in the axoplasm of unmyelinated peripheral nerves, whereas the localization of alpha E-catenin in the peripheral nervous system has not yet been reported [24].
• Introduction of an extra chromosome 2, carrying a wild type hMSH6 gene, restores post-replicative mismatch repair and also prevents the frequent inactivation of the remaining wild type CTNNA1 allele [25].

Analytical, diagnostic and therapeutic context of CTNNA1

• Immunoprecipitation with E-cadherin and Western blot analysis revealed that PC 9 cells did not express alpha-catenin, a cadherin-associated protein, suggesting that this was the cause of the cadherin dysfunction in the cell line [26].
• By fluorescence in situ hybridization the pseudogene was mapped to human chromosome 5q22 and the alpha E-catenin gene to the formerly disputed locus 5q31 [23].
• By electron microscopy using immunocytochemical methods, alpha E-catenin immunoreactivities were generally detected in the Schwann cell cytoplasm of unmyelinated nerve and the outer loop of myelinated nerve [24].

References