Disease:A chromosomal rearrangement involving CTNNB1 may be a cause of salivary gland pleiomorphic adenomas (PA) [181030]. Pleiomorphic adenomas are the most common benign epithelial tumors of the salivary gland. Translocation t (3;8) (p21;q12) with PLAG1. ,Disease:Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types , including colon cancers , ovarian and prostate carcinomas , hepatoblastoma (HB) , hepatocellular carcinoma (HCC) . HBs are malignant embryonal tumors mainly affecting young children in the first three years of life. ,Disease:Defects in CTNNB1 are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant , invasive embryonal tumor of the cerebellum with a preferential manifestation in children. ,Disease:Defects in CTNNB1 are a cause of pilomatrixoma (PTR) [MIM:132600]; a common benign skin tumor. ,Disease:Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:114500]. ,Disease:Defects in CTNNB1 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease , which is a principal determinant of outcome. ,Function:Involved in the regulation of cell adhesion and in signal transduction through the Wnt pathway. ,online information:Beta-catenin entry ,PTM:EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. ,PTM:Phosphorylation by GSK3B requires prior phosphorylation of Ser-45 by another kinase. Phosphorylation proceeds then from Thr-41 to Ser-37 and Ser-33. ,PTM:Ubiquitinated by a E3 ubiquitin ligase complex containing UBE2D1 , SIAH1 , CACYBP/SIP , SKP1A , APC and TBL1X (Probable) . Its ubiquitination leads to its subsequent proteasomal degradation. ,similarity:Belongs to the beta-catenin family. ,similarity:Contains 12 ARM repeats. ,subcellular location:Cytoplasmic when it is unstabilized (high level of phosphorylation) or bound to CDH1. Translocates to the nucleus when it is stabilized (low level of phosphorylation) . Interaction with GLIS2 and MUC1 promotes nuclear translocation. ,subunit:Two separate pools are found in the cytoplasm: one is PSEN1/cadherin/catenin complex which anchors to the actin cytoskeleton. The other pool is part of a large complex containing AXIN1 , AXIN2 , APC , CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. Wnt-dependent activation of DVL antagonizes the action of GSK3B. When GSK3B activity is inhibited the complex dissociates , CTNNB1 is dephosphorylated and is no longer targeted for destruction. The stabilized protein translocates to the nucleus , where it binds TCF/LEF-1 family members , TBP , BCL9 and possibly also RUVBL1 and CHD8. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding (By similarity) . Interacts with TAX1BP3 (via the PDZ domain) ; this interaction inhibits the transcriptional activity of CTNNB1 (By similarity) . Interacts with AJAP1 , BAIAP1 , CARM1 , CTNNA3 , CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2 and MUC1. Interacts with SLC30A9. Interacts with XIRP1 (By similarity) . Interacts with PTPRU (via the cytoplasmic juxtamembrane domain) . ,tissue specificity:Expressed in several hair follicle cell types: basal and peripheral matrix cells , and cells of the outer and inner root sheats. Expressed in colon. ,
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