Aberrant activation of Wnt/beta-catenin signaling is recognized as a critical factor in the etiology of colorectal cancer. Evidence has suggested that dysregulated beta-catenin activity is associated with the majority of colon cancers via activation of the expression of Wnt regulated oncogenes. In the nucleus, beta-catenin regulates transcription by recruiting additional coactivators. These coactivators all have distinct and unique functions on Wnt/beta-catenin target gene activation. Here we report two coactivators for beta-catenin-mediated transcription: CCAR1 (Cell Cycle and Apoptosis Regulator 1) and CARM1 (coactivator-associated-protein-arginine-methyltransferase 1). We show that both CCAR1 and CARM1 interact with beta-catenin and positively modulate beta-catenin-mediated gene expression. In colorectal cancer cells, which have constitutively high Wnt/beta-catenin activity, depletion of CCAR1 or CARM1 inhibits the expression of Wnt/beta-catenin-mediated oncogenes and suppresses ...
Aberrant beta-catenin expression as determined by assessment of its subcellular localization constitutes a surrogate marker of Wnt signalling pathway activation and has been reported in a subset of breast cancers. The association of beta-catenin/Wnt pathway activation with clinical outcome and the mechanisms leading to its activation in breast cancers still remain a matter of controversy. The aims of this study were to address the distribution of beta-catenin expression in invasive breast cancers, the correlations between beta-catenin expression and clinicopathological features and survival of breast cancer patients, and to determine whether aberrant beta-catenin expression is driven by CTNNB1 (beta-catenin encoding gene) activating mutations. Immunohistochemistry was performed on a tissue microarray containing 245 invasive breast carcinomas from uniformly treated patients, using two anti-beta-catenin monoclonal antibodies. Selected samples were subjected to CTNNB1 exon 3 mutation analysis by ...
SMAD4 has been suggested to inhibit the activity of WNT/beta-catenin signaling pathway in cancer. However, the mechanism by which SMAD4 antagonizes WNT/beta-catenin signaling in cancer remains largely unknown. Aurora A kinase (AURKA), which is frequently overexpressed in cancer, increases the transcriptional activity of beta-catenin/T cell factor (TCF) complex by stabilizing beta-catenin through the inhibition of GSK-3beta. Here, SMAD4 modulated AURKA in a TGF-beta-independent manner. Overexpression of SMAD4 significantly suppressed AURKA function including colony formation, migration, and invasion of cell lines. In addition, SMAD4 bound to AURKA, induced degradation of AURKA by the proteasome. A luciferase activity assay revealed that the transcriptional activity of the beta-catenin/TCF complex was elevated by AURKA, but decreased by SMAD4 overexpression. Moreover, target gene analysis showed that SMAD4 abrogated the AURKA-mediated increase of beta-catenin target genes. However, this inhibitory ...
In the canonical Wnt signaling pathway, beta-catenin activates target genes through its interactions with Tcf/Lef-family transcription factors and additional transcriptional coactivators. The crystal structure of ICAT, an inhibitor of beta-catenin-mediated transcription, bound to the armadillo repeat domain of beta-catenin, has been determined. ICAT contains an N-terminal helilical domain that binds to repeats 11 and 12 of beta-catenin, and an extended C-terminal region that binds to repeats 5-10 in a manner similar to that of Tcfs and other beta-catenin ligands. Full-length ICAT dissociates complexes of beta-catenin, Lef-1, and the transcriptional coactivator p300, whereas the helical domain alone selectively blocks binding to p300. The C-terminal armadillo repeats of beta-catenin may be an attractive target for compounds designed to disrupt aberrant beta-catenin-mediated transcription associated with various cancers. ICAT inhibits beta-catenin binding to Tcf/Lef-family transcription factors ...
beta Catenin, clone: 15B8, eBioscience™ 100μg; Unconjugated beta Catenin, clone: 15B8, eBioscience™ Primary Antibodies Cas to Caz
By means of the fluorescent differential display method, we isolated novel mouse and human genes, Drctnnb1a and DRCTNNB1A, the expression levels of which were inversely correlated to the amount of β-catenin present in cells. Recent reports have identified a number of mammalian genes including c-myc (6) , cyclin D1 (7) , matrilysin (8) , WISP (9) , c-jun, fra-1, uPAR, ZO-1 (10) , and NBL4 (11) that are regulated by stabilization and activation of β-catenin. In Xenopus or Drosophila, target genes for Wnt signaling include the nodal-related 3 gene, Xnr3 (17) , a member of the transforming growth factor-β superfamily, and homeobox genes engrailed (18) , goosecoid, siamois (17) , twin (19) , ultrabithorax (20) , and fibronectin (21) . Among those reported molecules, all but ZO-1 appeared to be up-regulated byβ -catenin through transactivation of Tcf/Lef transcription factors. Hence, DRCTNNB1A is only the second gene to be identified as down-regulated by the accumulation of β-catenin. ...
The PNU-74654 (PNU) compound is a non-FDAapproved drug which prevents that Tcf from binding to beta-catenin, acting as a Wnt/beta-catenin antagonist. In NCI-H295 cells,PNU-74654 significantly decreases cell proliferation 96 h after treatment, increases early and late apoptosis, decreases nuclear betacatenin accumulation, impairs CTNNB1/beta-catenin expression and increases betacatenin target genes 48 h after treatment. No effects are observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreases cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreases SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impairs corticosterone secretion 24 h after treatment but does not decrease cell viability[2]. ...
Billin et al. (23) observed that TSA activated TOPflash reporter activity in HEK293 cells in the presence and absence of exogenous β-catenin and LEF1, and provided evidence that HDAC1 switches LEF1 from a repressor to a transcriptional activator. Our results confirm that TSA increases TOPflash reporter activity, and demonstrate that the effect of HDAC1 on LEF1 can be extended to TCF4, the major form of TCF/LEF in colonic mucosa. Thus, under certain circumstances, HDAC1 might influence whether TCF4 acts as a transcriptional activator or repressor in the Wnt signaling pathway. The present results also show that TOPflash reporter activity can be used as an indirect measure of HDAC activity, with an increase in reporter activity corresponding to a decrease in HDAC activity in cells treated with TSA or SFN.. SFN is an effective cancer chemopreventive agent in several animal models (10, 11, 12) and is thought to induce phase 2 detoxification enzymes through the interaction of Nrf-2 with the ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Kim B، Koo H، Yang S، Bang S، Jung Y، Kim Y، Kim J، Park J، Moon RT، Song K، Lee I (June 2006). "TC1(C8orf4) correlates with Wnt/beta-catenin target genes and aggressive biological behavior in gastric cancer". Clinical Cancer Research. 12 (11 Pt 1): 3541-8. PMID 16740781. doi:10.1158/1078-0432.CCR-05-2440. ...
Sigma-Aldrich offers abstracts and full-text articles by [Laurent Pangon, Dessislava Mladenova, Lauren Watkins, Christa Van Kralingen, Nicola Currey, Sam Al-Sohaily, Patrick Lecine, Jean-Paul Borg, Maija R J Kohonen-Corish].
Beta-catenin is a multifunctional protein involved both in cell adhesion and in activation of transcription. Calcium-dependent intercellular adhesion transmembrane glycoprotein E-cadherin interacts by its cytoplasmic domain with reciprocally bound alpha, beta and gamma catenin. Beta-catenin links this complex through alpha-actinin to the cytoskeleton. Functional cadherin-catenin system is important for invasiveness of tumour cells. Beta-catenin level in cytoplasm is controlled by glycogen synthase kinase-3 beta. When activity of this kinase is blocked (e.g. by excessive stimulation of Wnt signaling pathway), hypophosphorylated stable form of beta-catenin accumulates in the cytoplasm, translocates to the nucleus and activates transcription of genes including those that are involved in cell cycle control. As a result, cell division and neoplastic transformation are promoted ...
14-3-3ζ has been found to associate with β-catenin (Tian et al., 2004). Later, it was found that Akt phosphorylates β-catenin at serine 552, which appears to enhance its interaction with 14-3-3ζ (Fang et al., 2007). In both cases, ectopic expression of 14-3-3ζ resulted in a moderate activation (two- to fourfold) of β-catenin-dependent transcription in TopFlash assays. We found that 14-3-3ζ enhances, whereas 14-3-3η and ε isoforms repress, β-catenin activation of the TopFlash reporter (Fig. 5 A). One possible explanation for this observation is that 14-3-3 overexpression exerts complex biological effects, which makes our interpretation of the TopFlash results difficult. In fact, 14-3-3 proteins have been shown to interact with a plethora of target proteins ranging from transcription factors to various signaling molecules (Dougherty and Morrison, 2004; Pozuelo Rubio et al., 2004). However, it is interesting to note that, consistent with our results (Fig. 7 C), ectopic expression of ...
In Xenopus, Wnt signals and their transcriptional effector beta-catenin are required for the development of dorsal axial structures. In zebrafish, previous loss-of-function studies have not identified an essential role for beta-catenin in dorsal axis
Chandran K C ♦ December 11, 2015 ♦ Leave a comment Scientists and cancer researchers have lately identified a particular biological molecule in our body known as BETA CATENIN as an ideal molecular target for anti-cancer therapy. They have been trying to develop drugs that could inhibit the over-expressions and aberrations of BETA CATENIN, which is recognized to be playing a big role in the biochemical processes underlying various types of cancers. Their attempts have not been so far successful, since any chemical compound they develop to target BETA CATENIN will inevitably have serious harmful effects upon the organism, since it is an essential biological molecule having diverse roles normal vital processes, and its complete inhibition may lead to be very dangerous consequences.. BETA CATENIN is a protein found as part of molecular complexes in forming cadherin cell adhesion factors of animal cells. It belongs to a family of biological compounds known as catenins, consisting of alpha ...
View Notes - 2011_Questions_Week_14_Answers from BIO 349 at University of Texas. 1. What happens when you deplete beta catenin in planarians? -The organism is no longer able to form a posterior side
Background: β‐Catenin is an important signaling molecule in the Wnt pathway that plays a key role in tumorgenesis. In the absence of Wnt signaling, the cytoplasmic level of β‐catenin is kept low due to rapid proteasomal‐mediated degradation of GSK3β phosphorylated β‐catenin. Activation of Wnt signaling leads to the inactivation of GSK3β, resulting in stabilization and accumulation of β‐catenin in the cytoplasm. Consequently, β‐catenin translocates into the nucleus, where it binds with members of the T‐cell factor (Tcf)/lymphocyte enhancer‐binding factor family of transcription factors and activates the expression of many target genes important for cancer development. Most colon cancers have activating mutations in the APC tumor suppressor or in β‐catenin itself. Furthermore, activating β‐catenin mutations have been found in a variety of other tumors such as melanomas, hepatocellular carcinomas, skin, breast, and prostate cancer, whereas β‐catenin is not activated ...
J:215487 Thompson CL, Ng L, Menon V, Martinez S, Lee CK, Glattfelder K, Sunkin SM, Henry A, Lau C, Dang C, Garcia-Lopez R, Martinez-Ferre A, Pombero A, Rubenstein JL, Wakeman WB, Hohmann J, Dee N, Sodt AJ, Young R, Smith K, Nguyen TN, Kidney J, Kuan L, Jeromin A,Kaykas A, Miller J, Page D, Orta G, Bernard A, Riley Z, Smith S, Wohnoutka P, Hawrylycz MJ, Puelles L, Jones AR, A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain. Neuron. 2014 Jul 16;83(2):309-23 ...
J:90567 Akiyama H, Lyons JP, Mori-Akiyama Y, Yang X, Zhang R, Zhang Z, Deng JM, Taketo MM, Nakamura T, Behringer RR, McCrea PD, de Crombrugghe B, Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 2004 May 1;18(9):1072-87 ...
Rabbit polyclonal beta Catenin (phospho Y489) antibody validated for WB, ICC and tested in Human. Immunogen corresponding to synthetic peptide
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
Zhang, J., G. J. Woodhead, S. K. Swaminathan, S. R. Noles, E. R. McQuinn, A. J. Pisarek, A. M. Stocker, C. A. Mutch, N. Funatsu, and A. Chenn, Cortical neural precursors inhibit their own differentiation via N-cadherin maintenance of beta-catenin signaling., Dev Cell, vol. 18, issue 3, pp. 472-9, 2010 Mar 16. PMCID: PMC2865854 PMID: 20230753 ...
Looking for online definition of Beta catenin in the Medical Dictionary? Beta catenin explanation free. What is Beta catenin? Meaning of Beta catenin medical term. What does Beta catenin mean?
Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene. Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha (TCRA) enhancer and confers maximal enhancer activity. LEF1 belongs to a family of regulatory proteins that share homology with high mobility group protein-1 (HMG1). LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia. It is also a promising potential drug target. Lymphoid enhancer-binding factor 1 has been shown to interact with: ALX4, AML-1, CTNNB1, EP300, MITF PIAS4, SMAD2, and SMAD3. GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000027985 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Milatovich A, Travis A, Grosschedl R, Francke U (Mar 1992). "Gene for lymphoid ...
US Biological Anti-Catenin, beta (Beta Catenin, Cadherin-associated Protein, Catenin beta 1, Catenin beta-1, CATNB, CTNNB, CTNNB1) SKU: C2069-51C()
We show that expression of stabilized β-catenin decreased neurite initiation and elongation in NGF-treated PC12 cells (Fig. 5). Several mechanisms could explain how stabilized β-catenin inhibits neurite outgrowth in PC12 cells. When β-catenin is stabilized by Wnt signals it can promote cadherin-mediated cell-cell adhesion (Hinck et al., 1994) in addition to Tcf/Lef-mediated transcription. Experiments expressing stabilized β-catenin in whole animals or in neuronal cultures directly contacting glial cells may mask the role of β-catenin in the APC complex with its role in adhesion (Yu and Malenka, 2004; Loureiro et al., 2001; Elul et al., 2003). Previous work on the role of β-catenin in branching of axons and dendrites uses neurons in direct cell-cell contact with a glial feeder layer, and β-catenin is thought to require N-cadherin for this effect (Yu and Malenka, 2003; Yu and Malenka, 2004). PC12 cells do not form distinct axons and dendrites (Greene et al., 1998) and, if treated with NGF ...
The Wnt signal transduction pathway is important in a wide variety of developmental processes as well as in the genesis of human cancer. Vertebrate Wnt pathways can be functionally separated into two classes, the canonical Wnt/beta-catenin pathway and the non-canonical Wnt/Ca2+ pathway. Supporting differences in Wnt signaling, gain of function of Wnt-1 in C57mg mouse mammary epithelial cells leads to their morphological transformation while loss of function of Wnt-5a leads to the same transformation. Many downstream target genes of the Wnt/beta-catenin pathway have been identified. In contrast, little is known about the Wnt/Ca2+ pathway and whether it regulates gene expression. To test the hypothesis that a specific cell line can respond to distinct Wnts with different patterns of gene expression, we over-expressed Wnt-5a and Rfz-2 in C57mg mammary epithelial cells and compared this cell line to C57mg cells over-expressing Wnt-1. These Wnts were chosen since previous studies suggest that C57mg cells
Akt-regulated pathways enhance cell division and cell survival. Metabolic regulation through Akt and its targets is important for insulin and insulin-like growth factor I-coupled responses. Inhibition of glycogen synthase kinase-3 by Akt-dependent phosphorylation promotes accumulation of β-catenin, which forms complexes with T-cell factor/lymphoid enhancer factor transcription factors and transcriptionally up-regulates cyclin D1, Myc, and other positive growth regulators. Cyclin D1 is also inhibited by glycogen synthase kinase-3 through effects on stability and localization (7) . Concomitantly, Akt phosphorylation of cyclin-dependent protein kinase inhibitors p21Cip1 and p27Kip1 interferes with negative growth regulation (3 , 8) .. Phosphorylation of Mdm2 by Akt enhances nuclear entry, which promotes ubiquitin-dependent proteolysis of p53, and impedes p53-dependent growth suppression and apoptosis (9) . Akt directly forestalls apoptosis by phosphorylation of proapoptotic Bad and caspase-9, ...
Catenin Beta 1, CTNNB are cell adhesion molecules called (p120*␠-catenin) cadherins (the (CDH1) E-cadherin/catenin complex) include the beta-catenins a multifunctional molecule Locus: 3p22.1 [§§; ^]. Neurons also exhibited a higher CTNNB/TCF pathway association (concentration versus accumulation) with cadherins; CAS-chromosome segregation 1-like (yeast) binds with E-cadherin but not with beta-catenin. Which interacts with (Tcf-T-cell factor where a…
A key component of the Wnt pathway, beta-catenin combines with alpha-catenin and regulates cell-cell adhesion. It also interacts with alpha-catenin in the nucleus.. The alpha-catenin component of this beta-catenin/alpha-catenin complex has an inhibitory effect on beta-catenin that helps keep tumor cell migration and invasion in check. This inhibition is lost, however, when the EGFR pathway is activated. Upon activation, beta-catenin becomes untethered from alpha-catenin and translocates to the cell nucleus, where it increases expression of key target genes involved in tumor cell invasion and metastasis.. New Pathway Regulates Beta-Catenin Transactivation. The M. D. Anderson-led team made a surprising discovery: Beta-catenin also can travel to the nucleus via activation of the EGFR pathway-and it does so independently of Wnt signaling or mutations. The newly described pathway disrupts the beta-catenin/alpha catenin complex through an EGFR-extracellular receptor kinase (ERK)-protein kinase CK2- ...
BCL9 and PYGO are beta-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in developing mouse forelimbs, BCL9 proteins sustain the action of beta-catenin in a largely PYGO-independent manner. Our genetic analyses implied that BCL9 necessitates other interaction partners in mediating its transcriptional output. We identified the transcription factor TBX3 as a candidate tissue-specific member of the beta-catenin transcriptional complex. In developing forelimbs, both TBX3 and BCL9 occupy a large number of Wnt-responsive regulatory elements, genome-wide. Moreover, mutations in Bcl9 affect the expression of TBX3 targets in vivo, and modulation of TBX3 abundance impacts on Wnt target genes transcription in a beta-catenin- and TCF/LEF-dependent manner. Finally, TBX3 overexpression exacerbates the metastatic potential of Wnt-dependent
beta-catenin destruction complex, beta-catenin-TCF7L2 complex, catenin complex, cell cortex, cell junction, cell periphery, cell-cell adherens junction, cell-cell junction, centrosome, cytoplasm
The canonical Wnt/beta-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5(-/-)) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5(-/-) mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5(-/-) mice, whereas
3.0.CO;2-P. PMID 10580987. McCrea PD, Turck CW, Gumbiner B (November 1991). "A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin". Science. 254 (5036): 1359-61. doi:10.1126/science.1962194. PMID 1962194. Kemler R (September 1993). "From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion". Trends in Genetics. 9 (9): 317-21. doi:10.1016/0168-9525(93)90250-l. PMID 8236461. Gottardi CJ, Peifer M (March 2008). "Terminal regions of beta-catenin come into view". Structure. 16 (3): 336-8. doi:10.1016/j.str.2008.02.005. PMC 2329800 . PMID 18334207. Xing Y, Takemaru K, Liu J, Berndt JD, Zheng JJ, Moon RT, Xu W (March 2008). "Crystal structure of a full-length beta-catenin". Structure. 16 (3): 478-87. doi:10.1016/j.str.2007.12.021. PMC 4267759 . PMID 18334222. Vleminckx K, Kemler R, Hecht A (March 1999). "The C-terminal transactivation domain of beta-catenin is necessary and sufficient for signaling by the LEF-1/beta-catenin complex ...
The canonical Wnt/beta-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5(-/-)) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5(-/-) mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5(-/-) mice, ...
Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling (By similarity). Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway. In Wnt signaling, probably facilitates the phosphorylation of CTNNB1 and APC by GSK3B. Likely to function as a tumor suppressor. Facilitates the phosphorylation of TP53 by HIPK2 upon ultraviolet irradiation. Enhances TGF-beta signaling by recruiting the RNF111 E3 ubiquitin ligase and promoting the degradation of inhibitory SMAD7 (By similarity). Also component of the AXIN1-HIPK2-TP53 complex which controls cell growth, apoptosis and development.
Cadherins play an important role in morphogenesis and have recently been implicated in the regulation of cell proliferation, however the mechanisms by which they function are poorly understood. In the vertebrate CNS, loss of ,italic,N-cadherin (N-cad),,/, results in impaired neuroepithelial integrity. Zebrafish ,italic,N-cad,,/, null mutants also exhibit a transient increase in neurons and in cell proliferation in the neural tube. Here, we investigate the cellular and molecular basis for this phenotype, using multiple ,italic,N-cad,,/, alleles with distinct molecular properties. We confirm that cell proliferation is enhanced in ,italic,N-cad,,/, mutants, but contrary to previous findings, we observe that the increase is sustained over multiple stages of development. At the cellular level, loss of ,italic,N-cad,,/, results in a shorter cell cycle. Furthermore, we demonstrate that hyperproliferation is not linked to abnormal beta-catenin localization, suggesting that Wnt signaling is not ...
Cadherins play an important role in morphogenesis and have recently been implicated in the regulation of cell proliferation, however the mechanisms by which they function are poorly understood. In the vertebrate CNS, loss of ,italic,N-cadherin (N-cad),,/, results in impaired neuroepithelial integrity. Zebrafish ,italic,N-cad,,/, null mutants also exhibit a transient increase in neurons and in cell proliferation in the neural tube. Here, we investigate the cellular and molecular basis for this phenotype, using multiple ,italic,N-cad,,/, alleles with distinct molecular properties. We confirm that cell proliferation is enhanced in ,italic,N-cad,,/, mutants, but contrary to previous findings, we observe that the increase is sustained over multiple stages of development. At the cellular level, loss of ,italic,N-cad,,/, results in a shorter cell cycle. Furthermore, we demonstrate that hyperproliferation is not linked to abnormal beta-catenin localization, suggesting that Wnt signaling is not ...
CG-001 is a selective Wnt/β-catenin signalling inhibitor with an IC50 of 3μM. ICG 001, a small molecule that down-regulates beta-catenin/T cell factor signaling by specifically binding to cyclic AMP response element-binding protein. ICG001 selectively ind
Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E-cadherin, guides the establishment of classical epithelial cell polarity and contributes to the control of migration, growth, and differentiation. These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton. The molecular basis for these interactions and their hierarchy of interaction remain controversial. We demonstrate a direct interaction between F-actin and alpha (E)-catenin, an activity not shared by either the cytoplasmic domain of E-cadherin or beta-catenin. Sedimentation assays and direct visualization by transmission electron microscopy reveal that alpha 1(E)-catenin binds and bundles F-actin in vitro with micromolar affinity at a catenin/G-actin monomer ratio of approximately 1:7 (mol/mol). Recombinant human beta-catenin can simultaneously bind to the alpha-catenin/actin complex but does not bind actin ...
The farnesoid X receptor (FXR) controls the synthesis and transport of bile acids (BAs). Mice lacking expression of FXR, designated Fxr-null, have elevated levels of serum and hepatic BAs and an increase in BA pool size. Surprisingly, at 12 months of age, male and female Fxr-null mice had a high incidence of degenerative hepatic lesions, altered cell foci and liver tumors including hepatocellular adenoma, carcinoma and hepatocholangiocellular carcinoma, the latter of which is rarely observed in mice. At 3 months, Fxr-null mice had increased expression of the proinflammatory cytokine IL-1beta mRNA and elevated beta-catenin and its target gene c-myc. They also had increased cell proliferation as revealed by increased PCNA mRNA and BrdU incorporation. These studies reveal a potential role for FXR and BAs in hepatocarcinogenesis.
The study, published online in the September 2011 edition of The Journal of Neuroscience, identified Sox17 as the gene that helps regulate the Wnt/beta-catenin signaling pathway during the transition of oligodendrocyte progenitor cells, or immature brain cells, to a more mature, differentiated state where they generate myelin.. "This is the first time the Sox17 gene has been identified as a regulator of the Wnt/beta-catenin pathway during myelination," said Li-Jin Chew, PhD, lead author of the study. "Our findings indicate that loss of Sox17 over-stimulates the Wnt/beta-catenin pathway and keeps oligodendrocyte progenitor cells from maturing and producing myelin, potentially causing developmental disabilities in developing babies and children.". Myelin is the protective material around the axons of neurons; in mass these types of ensheathed neurons are collectively called white matter. White matter serves as the primary messaging "network" that conducts signals rapidly between gray matter areas. ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Negative regulator of the canonical Wnt signaling pathway involved in neuroectodermal patterning. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex ...
The Wnt/β-catenin signaling pathway plays an important role in renal development and is reexpressed in the injured kidney and other organs. β-Catenin signaling is protective in acute kidney injury (AKI) through actions on the proximal tubule, but the current dogma is that Wnt/β-catenin signaling promotes fibrosis and development of chronic kidney disease (CKD). As the role of proximal tubular β-catenin signaling in CKD remains unclear, we genetically stabilized (i.e., activated) β-catenin specifically in murine proximal tubules. Mice with increased tubular β-catenin signaling were protected in 2 murine models of AKI to CKD progression. Oxidative stress, a common feature of CKD, reduced the conventional T cell factor/lymphoid enhancer factor-dependent β-catenin signaling and augmented FoxO3-dependent activity in proximal tubule cells in vitro and in vivo. The protective effect of proximal tubular β-catenin in renal injury required the presence of FoxO3 in vivo. Furthermore, we identified ...
Background: The Wnt/beta-catenin signaling pathway plays a key role in stem cell maintenance in the colorectum. Rare high penetrance genetic mutations in components of this pathway result in familial colorectal cancer, yet the impact of common, germline variants remains unknown. Methods: We assessed 172 variants in 26 genes from the Wnt/beta-catenin pathway in 809 CRC cases and 814 healthy controls, followed by replication of the top findings in another 691 cases and 775 controls. In silico informatic tools were used to predict functional effects of variants. Results: Eighteen SNPs in the pathway were significantly associated with CRC risk (P ,0.05) in the discovery phase. We observed a significant dose-response increase in CRC risk by number of risk genotypes carried (P = 4.19 x 10-8). Gene-based analysis implicated CSNK1D (P = 0.014), FZD3 (P = 0.023), and APC (P = 0.027) as significant for CRC risk. In the replication phase, FZD3:rs11775139 remained significantly associated with reduced risk ...
(a) Nuclear suprabasal beta-catenin (β-catenin) staining expression in all layers of epidermis except the parakeratotic and cornified layers of a psoriasis les
LEF1 antibody [1C3.1D10] (lymphoid enhancer-binding factor 1) for WB. Anti-LEF1 mAb (GTX12033) is tested in Human samples. 100% Ab-Assurance.
1I7X: The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin.