Anti-β-Catenin, clone 5H10

P35222

FUNCTION: SwissProt: P35222 # Involved in the regulation of cell adhesion and in signal transduction through the Wnt pathway.
SIZE: 781 amino acids; 85497 Da
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 DUPLIN. Binds CTNNBIP and EP300. CTNNB1 forms a ternary complex with LEF1 and EP300 that is disrupted by CTNNBIP1 binding (By similarity). Interacts with the PDZ domain of TAX1BP3; this interaction inhibits the transcriptional activity of CTNNB1 (By similarity). Interacts with AJAP1, BAIAP1, CARM1, CTNNA3, CXADR and PCDH11Y. Binds SLC9A3R1. Interacts with GLIS2. Interacts with SLC30A9 (By similarity).
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=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 promotes nuclear translocation.
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.
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. & EGF stimulates tyrosine phosphorylation. Phosphorylation on Tyr-654 decreases CDH1 binding and enhances TBP binding. & 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.
DISEASE: "SwissProt: P35222 # 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. & Defects in CTNNB1 are a cause of pilomatrixoma (PTR) [MIM:132600]; a common benign skin tumor. & 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. & 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."
SIMILARITY: SwissProt: P35222 ## Belongs to the beta-catenin family. & Contains 12 ARM repeats. ... hide » see more »

NM_001098209.1

Beta-catenin is an adherens junction protein. Adherens junctions (AJs; also called the zonula adherens) are critical for the establishment and maintenance of epithelial layers, such as those lining organ surfaces. AJs mediate adhesion between cells, communicate a signal that neighboring cells are present, and anchor the actin cytoskeleton. In serving these roles, AJs regulate normal cell growth and behavior. At several stages of embryogenesis, wound healing, and tumor cell metastasis, cells form and leave epithelia. This process, which involves the disruption and reestablishment of epithelial cell-cell contacts, may be regulated by the disassembly and assembly of AJs. AJs may also function in the transmission of the 'contact inhibition' signal, which instructs cells to stop dividing once an epithelial sheet is complete.[supplied by OMIM] ... hide » see more »

Anti-β-Catenin, clone 5H10

The transmembrane, calcium dependent molecule E-cadherin is considered to be one of the key molecules in the formation of the intercellular junctional complex and establishment of polarity in epithelial cells. Catenins, the alpha-subunit (102 kDa), beta-subunit (88 kDa) and gamma-subunit (82 kDa), [reviewed in Takeichi, 1991] are a group of proteins that interact with the intercellular domain of E-cadherin, resulting in complexes of E-cadherin/beta-catenin/alpha-catenin or E-cadherin/gamma-catenin/alpha-Catenin (Hinck et al., 1994). Beta-catenin, the vertebrate homologue of Drosophila segment polarity gene armadillo, and key element of the Wnt signal transduction pathways, is important in embryogenesis, cell transformation, and intercellular adhesion including the adhesion, motility and metastasis of cancer cells. Thus, catenin protein expression, regulation and localization are potentially important markers to predict motility and invasiveness of epithelial neoplasms. The regions of both alpha- and beta-catenin, located on 5q21-22 and 3p21, have been shown to be involved in the development of certain tumors (see Jiang, 1996; Schlosshauer et al., 2002) and reduced expressions of both alpha- and beta-catenin have been described in various tumors including breast carcinoma (Hashizume et al, 1996). Besides adhesion functions, beta-catenin binds to the tumor suppressor gene APC. APC mutation disturbs the equilibrium and cytoplasmic levels of free beta-catenin level in the cell and may have a role in tumorigenesis.

5H10

Recognizes an epitope in the carboxy terminus, amino acids 758-771, of human beta-catenin.

• Immunocytochemistry
• Immunohistochemistry
• Immunohistochemistry (Paraffin)
• Immunoprecipitation
• Western Blotting

Immunohistochemistry: Low cross-linking fixatives are recommended. Histochoice fixative is effective. Formalin and PFA are effective, however may show weaker staining.

Immunohistochemistry on formalin fixed paraffin embedded tissues requires light fixations and citric acid/microwave antigen recovery for staining; In brief, sections of 2μm thickness were treated after deparaffinization with 0.3% hydrogen peroxide in methanol for 30 minutes to inhibit endogenous peroxidase and washed with TBS solution (Tris-buffered saline pH 7.6). To enhance antigen retrieval, sections were microwave-pretreated in 0.01 M citrate buffer solution at 750 W for a 3 minute-cycle period repeated three times; amplified detection methods are recommended.

Immunocytochemistry: Effective for A431 and HT1080 cell lines with acetone or methanol, or light PFA fixation.

Immunoblotting

Immunoprecipitation

Optimal working dilutions must be determined by end-user.

• Human
• Rat

IgG1

Produced by immunization with recombinant human beta-catenin.

94 kDa

A431 and HT1080 cell line extracts

Protein A Purified IgG in liquid at 1 mg/mL in 0.02M PB with 0.25M NaCl, pH 7.6, containing 0.1% sodium azide.

Maintain for 1 year at 2–8°C from date of shipment. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.

• CTNNB1
• FLJ25606
• CTNNB
• Beta-catenin
• PRO2286
• FLJ37923
• DKFZp686D02253

Epigenetics & Nuclear Function

Transcription Factors

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Chemicon (Millipore)

Pur

1.0 mg/mL

Monoclonal Antibody

Purified

Mouse

Protein A Purified