Regulates beta catenin. Medical search. Frequent questions

The Wnt/beta-catenin signaling pathway is critical in both cellular proliferation and organismal development. (duke.edu)
Using a directed RNAi screen we find that protein phosphatase 1 (PP1), a ubiquitous serine/threonine phosphatase, is a novel potent positive physiologic regulator of the Wnt/beta-catenin signaling pathway. (duke.edu)
Specific inhibition of PP1 in this pathway may offer therapeutic approaches to disorders with increased beta-catenin signaling. (duke.edu)
Furthermore, we showed that DAB2IP negatively regulated ATG9B expression by blocking the Wnt/β-catenin pathway. (nature.com)
To enhance the benefit of TMZ and avoid therapeutic resistance, effective combination strategies were tested using a small molecule inhibitor blocking the Wnt/β-catenin pathway in addition to TMZ. (nature.com)
The Wnt/β-catenin pathway plays a critical role in embryonic development, maintenance of multipotent progenitor cell populations and proliferation of many tissue types [1] , [2] . (plos.org)
The protein inhibits GSK-3-mediated phosphorylation of beta-catenin and positively regulates the Wnt signaling pathway. (nih.gov)
Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/β-catenin pathway in hepatocellular carcinoma cells. (nih.gov)
As part of the cell-signaling pathway, beta-catenin interacts with other proteins to control the activity (expression) of particular genes, which helps promote cell proliferation and differentiation. (medlineplus.gov)
The Wnt pathway mediates the biological processes of the canonical or non-canonical pathway, depending on the involvement of β-catenin in signal transduction. (chemdiv.com)
The recently described role of the Wnt/β-catenin pathway in the regulation of immune cell infiltration of microenvironment tumor resumes interest because of its potential impact to rection of immune therapy. (chemdiv.com)
This article presents the roles of the Wnt/β-catenin pathway in cancer and current therapeutic strategies involving this pathway. (chemdiv.com)
Nussе and Varmus identified components of the Wnt/β-catenin pathway in 1982 in a study of oncogenic breast tumor viral diseases (MMTV) [1]. (chemdiv.com)
In embryonic Xenopus development, Rap2 is necessary for the Wnt/beta-catenin signaling pathway. (nih.gov)
Finally, we found that PAK3 regulated EMT-related molecule expression and EMT-related TGF-β/smad signaling pathway. (jcancer.org)
Mechanistically, SP1 targeted miR-200b-3p to inhibit Wnt/β-catenin pathway. (biomedcentral.com)
MiR-200b-3p depletion rescued the promoting effect of SP1 on SONFH cell model by activating Wnt/β-catenin pathway. (biomedcentral.com)
SP1 targeted miR-200b-3p and inhibited Wnt/β-catenin signaling pathway. (biomedcentral.com)
Here, we have investigated whether cross-talk may exist between the Wnt/beta-catenin signaling pathway and lama5 during the branching process in SMG development. (bvsalud.org)
The roles and possible interactions of the Wnt/beta-catenin signaling pathway, FGF signaling, and lama5 in the branching process were investigated by morphogenesis assays and gene expression patterns. (bvsalud.org)
We conclude that the Wnt/beta-catenin signaling pathway acting downstream of FGF signaling can serve as a negative regulatory mechanism in the process of SMG branching morphogenesis through Lama5. (bvsalud.org)
Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. (bvsalud.org)

The central effector of canonical Wnt signaling, β-catenin (CTNNB1), is a multifunctional protein, and has been extensively studied with respect to its roles in cell-cell adhesion and in regulation of Wnt-driven transcription. (nih.gov)
Loss-of-function mutations in APC or AXIN or activating mutations in the gene encoding β-catenin, CTNNB1 , lead to aberrant activation of Wnt/β-catenin signaling and have been causally linked to tumorigenesis of the colon, liver and skin [1] , [4] . (plos.org)
CTNNB1 phosphorylation regulates insulin internalization. (proteopedia.org)
The CTNNB1 gene provides instructions for making a protein called beta-catenin. (medlineplus.gov)
CTNNB1 gene mutations lead to an abnormally stable beta-catenin protein that is not broken down when it is no longer needed. (medlineplus.gov)
Excess beta-catenin, whether caused by CTNNB1 or APC gene mutations, promotes uncontrolled growth and division of cells, allowing the formation of desmoid tumors. (medlineplus.gov)
Homo sapiens catenin beta 1 (CTNNB1), transcript variant 1, mRNA. (origene.com)

Scholars@Duke publication: Protein phosphatase 1 regulates assembly and function of the beta-catenin degradation complex. (duke.edu)
However, how the beta-catenin degradation complex is inhibited upon Wnt activation remains unclear. (duke.edu)
In the absence of Wnt ligands, a complex containing APC, AXIN and GSK3 phosphorylates β-catenin, marking it as a substrate for ubiquitination by β-TrCP and subsequent proteasomal degradation. (plos.org)
In addition to ligand-regulated degradation of β-catenin, Wnt signaling is antagonized by extracellular factors that inhibit the ability of Wnt ligands to bind to Fzd and initiate signaling, such as the secreted frizzled-related proteins (SFRP1, WNT inhibitory factor (WIF) and dickkopf (DKK) [3] . (plos.org)
Keratin 19 interacts with GSK3beta to regulate its nuclear accumulation and degradation of cyclin D3. (addgene.org)
In last funding cycle, we have published that Fam13a promotes the degradation of beta-catenin and inhibits cell growth. (hhs.gov)
The tumor suppressor protein APC forms the core of a cytoplasmic complex which binds ß-catenin and targets it for degradation in the proteasome. (hubrecht.eu)

Here, a novel mass spectrometry-based proteomics technique in colorectal cancer cells expressing stabilized β-catenin, was used to identify a protein-protein interaction between β-catenin and DNA methyltransferase I (Dnmt1) protein, the primary regulator of DNA methylation patterns in mammalian cells. (nih.gov)
Dnmt1 and β-catenin strongly colocalized in the nuclei of colorectal cancer cells, and the interaction is mediated by the central domain of the Dnmt1 protein. (nih.gov)
Dnmt1 protein abundance is dependent upon the levels of β-catenin, and is increased in cells expressing stabilized mutant β-catenin. (nih.gov)
In addition, lysine-specific demethylase 1 (LSD1/KDM1A), a regulator of DNMT1 stability, was identified as a component of the Dnmt1-β-catenin protein complex and perturbation of the Dnmt1-β-catenin interaction altered DNA methylation. (nih.gov)
2 Protein interactions are critical to the stability, localization and activity of b-catenin, and we recently performed the first proteomic analyses of the b-catenin interactome in myeloid cells. (haematologica.org)
In order to idenitfy appropriate cell lines in which to study b-catenin:WT1 interplay we first performed a screen of myeloid cell lines to examine b-catenin and WT1 protein expression. (haematologica.org)
WT1 is an RNA-binding protein, 6 and β-catenin has also been shown to bind RNA, 7 so to confirm this interaction was not indirect via RNA binding we repeated WT1 Co-IP (with or without CHIR99021) after first confirming complete digestion of RNA through RNase A pre-treatment of cell lysates ( Figure 1E ). (haematologica.org)
We further wanted to ascertain whether this protein interaction was direct using recombinant versions of purified b-catenin and WT1 protein but failed to detect any association ( Online Supplementary Figure S1B, C ). This suggested that perhaps the interaction is mediated through a post-translational modification, common partners such as WTX, 8 or cellular structures like DNA, given their well-documented roles in transcription. (haematologica.org)
A) Immunoblot of myeloid leukemia cell lines showing the relative level of b-catenin (~92 kDa) and WT1 (~50 kDa) protein, with b-actin (42 kDa) used to assess protein loading. (haematologica.org)
The protein produced from the APC gene helps regulate levels of beta-catenin in the cell. (medlineplus.gov)
When beta-catenin is no longer needed, the APC protein attaches (binds) to it, which signals for it to be broken down. (medlineplus.gov)
Mutations in the APC gene that cause desmoid tumors lead to a short APC protein that is unable to interact with beta-catenin. (medlineplus.gov)
β-Catenin is a fascinating protein with many important cellular and developmental functions. (chemdiv.com)
The roles of b-catenin are 'classically' defined: as an adhesion protein and as a signaling protein, transducing extracellular signals to the nucleus to modify gene expression. (chemdiv.com)
β -catenin has many binding partners that mediate a diverse set of cellular functions, and the protein probably acts as a 'hub' on which many cellular signaling networks impinge. (chemdiv.com)
This library represents a selection of drug-like compounds aimed at modulating protein-protein interaction (PPI) of β-catenin with different proteins involved in significant physiological processes. (chemdiv.com)
Both isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) and Traf2- and Nck-interacting kinase (TNIK) are putative effectors of Rap2 in mediating the activation of c-Jun N-terminal kinase (JNK) to regulate the actin cytoskeleton. (nih.gov)
The LAP [leucine-rich and postsynaptic density-95/Discs large/zona occludens-1 (PDZ)] protein erbin and δ-catenin, a component of the cadherin-catenin cell adhesion complex, are highly expressed in neurons and associate through PDZ-mediated interaction, but have incompletely characterized neuronal functions. (jneurosci.org)

Here we identify CSNK1E , the gene encoding casein kinase 1 epsilon (CK1ε) as required specifically for the proliferation of breast cancer cells with activated β-catenin and confirm its role as a positive regulator of β-catenin-driven transcription. (plos.org)
14-3-3sigma regulates beta-catenin-mediated mouse embryonic stem cell proliferation by sequestering GSK-3beta. (addgene.org)
Overall, the present study determined the roles and mechanism of the VIM‑AS1/IGF2BP2/HMGCS1 axis in regulating proliferation and enzalutamide sensitivity of prostate cancer cells and suggested that VIM‑AS1 may serve as a novel therapeutic target for the treatment of patients with CRPC. (spandidos-publications.com)

Wnt-regulated changes in axin phosphorylation, mediated by PP1, may therefore determine beta-catenin transcriptional activity. (duke.edu)

We show that short hairpin RNA-mediated knockdown of erbin and knockdown or genetic ablation of δ-catenin severely impaired dendritic morphogenesis in hippocampal neurons. (jneurosci.org)
These results suggest a critical role for erbin in regulating dendritic morphogenesis by maintaining appropriate localization of δ-catenin. (jneurosci.org)
Finally, we show that Wnt/beta-catenin signaling regulates branching morphogenesis through Lama5. (bvsalud.org)

Once stabilized, β-catenin accumulates and translocates to the nucleus, where it complexes with TCF/LEF to activate transcription of target genes, such as MYC and CCND1 . (plos.org)
As a result, beta-catenin is not broken down and, instead, accumulates in cells. (medlineplus.gov)
In APC-deficient colon carcinoma cells, we demonstrated that ß-catenin accumulates and is constitutively complexed with the TCF family member TCF4, providing a molecular explanation for the initiation of colon cancer (5). (hubrecht.eu)

Canonical Wnt/β-catenin signaling is initiated by binding of Wnt ligands to Frizzled (Fzd)-LRP5/6 receptor complexes, leading to inactivation of the destruction complex and stabilization of β-catenin. (plos.org)
Speaking more specifically, β-catenin is an integral structural component of cadherin-based adhesive junctions as well as it a key nuclear effector of canonical in nucleus Wnt signaling. (chemdiv.com)

Tyrosine phosphorylation regulates the adhesions of ras-transformed breast epithelia. (rupress.org)

The data suggest that PP1 controls Wnt signaling through interaction with, and regulated dephosphorylation of, axin. (duke.edu)
As shown in Figure 1F-H, the b-catenin:WT1 interaction remained in K562, HEL and KG-1 cells under both basal (DMSO) and stimulated (CHIR99021) Wnt signaling. (haematologica.org)
A representative example of a 'druggable' 'hot spots' included specific topological features of the β -catenin interaction. (chemdiv.com)
In particular, decreased tyrosine phosphorylation of beta-catenin is accompanied by increased interaction with both E-cadherin and the detergent insoluble cytoskeletal fraction. (rupress.org)

The dendritic phenotype observed after erbin depletion is rescued by overexpression of δ-catenin and requires a domain in δ-catenin that has been shown to regulate dendritic branching. (jneurosci.org)
Knockdown of δ-catenin cannot be rescued by overexpression of erbin, indicating that erbin is upstream of δ-catenin. (jneurosci.org)

PP1 expression synergistically activates, and inhibition of PP1 inhibits, Wnt/beta-catenin signaling in Drosophila and mammalian cells as well as in Xenopus embryos. (duke.edu)
In some cases, Sox17 and β-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses β-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. (xenbase.org)

Vertebrate catenins contain a large number of Arm-domains including 3 subfamilies: β-tencains, p120 and plakophilins 1 and 3. (chemdiv.com)
The ras-transformed cells reveal elevated phosphotyrosine in many proteins, including beta-catenin and p120 Cas. (rupress.org)
Whereas in the normal cells beta-catenin is found in association with E-cadherin, p120 Cas is not. (rupress.org)
tyrosine-phosphorylated p120 Cas, but not tyrosine-phosphorylated beta-catenin, now is detected in E-cadherin complexes. (rupress.org)
These results suggest that elevated tyrosine phosphorylation of proteins such as beta-catenin and p120 Cas contribute to the altered adherens junctions of ras-transformed epithelia. (rupress.org)
δ-Catenin belongs to the p120 catenin (p120ctn) family of catenins and binds to the cytoplasmic domains of type 1 and 2 cadherins at a membrane proximal region that is not involved in binding of either β-catenin or plakoglobin. (jneurosci.org)

The molecular weight of proteins were 102, 88 and 80 kDa, so they were named α, β and γ-catenin. (chemdiv.com)

The molecule apparently does so by regulating levels of beta-catenin in bone cells known as osteoblasts. (smithsonianmag.com)
β-catenin is a multipurpose and evolutionarily conserved molecule that plays a critical role by metazoans in a variety of processes in development and homeostasis. (chemdiv.com)
β-catenin belongs to the catenin molecule family. (chemdiv.com)

Upon Wnt signaling, ß-catenin binds and activates nuclear TCFs by providing a trans-activation domain. (hubrecht.eu)

Wnt/β-catenin signaling is a branch of a functional network that is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. (chemdiv.com)

An imbalance in the structural and signaling properties of β-catenin often leads to disease and unregulated growth associated with cancer and metastasis. (chemdiv.com)

APS regulated osteocyte autophagy and apoptosis via SP1/miR-200b-3p axis and activated Wnt/β-catenin signaling, thereby alleviating SONFH, shedding new insights for therapy of SONFH. (biomedcentral.com)

However, depletion of beta-catenin failed to completely revert phenotype seen in Fam13-/- mice, suggesting additional pathways regulated by FAM13A may play a role in the lung repair/regeneration process. (hhs.gov)
MiR-200b-3p depletion overturned effects of overexpressed SP1 via Wnt/β-catenin. (biomedcentral.com)

Knockdown of erbin results in alterations in localization of δ-catenin. (jneurosci.org)

Although mutations in these same genes have not been observed as recurrent genetic events in breast tumors, there is strong evidence implicating Wnt/β-catenin activity in breast tumorigenesis. (plos.org)

DAB2IP sensitized GBM to TMZ and suppressed TMZ-induced autophagy by negatively regulating ATG9B expression. (nature.com)
Recently, APS was reported to improve SONFH via regulating cell autophagy and apoptosis [ 9 ]. (biomedcentral.com)

beta-Catenin regulates P-cadherin expression in mammary basal epithelial cells. (igbmc.fr)
We also find that expression of CK1ε is able to promote oncogenic transformation of human cells in a β-catenin-dependent manner. (plos.org)
Expression of Frat1 correlates with expression of β-catenin and is associated with a poor clinical outcome in human SCC and AC. (nih.gov)
We observed a statistically significant correlation between b-catenin and WT1 expression across 16 myeloid cell lines, with 50% (8/16) co-expressing b-catenin and WT1 to varying degrees ( Figure 1A , B). There was no particular association of this correlation with cell line morphology or genotype. (haematologica.org)
Key genes are color coded based on regional expression from fate map in (E). (E) Enriched expression of Sox17 -regulated transcripts. (xenbase.org)
High expression of PAK3 enhances the invasion of HCC and regulates EMT, suggesting that PAK3 may be a potential target for the treatment of HCC. (jcancer.org)
Fig. 2 The expression of vpp1 is regulated by hhex . (xenbase.org)
Laminin subunit beta 1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. (bvsalud.org)
U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. (bvsalud.org)

DBC1 promotes castration-resistant prostate cancer by positively regulating DNA binding and stability of AR-V7. (cancerindex.org)

Conversely, the Dnmt1 regulates the levels of nuclear β-catenin and β-catenin/TCF-driven transcription. (nih.gov)

Our findings establish Sox17 as a tissue -specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/β-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and β-catenin/Tcf transcriptional complexes. (xenbase.org)

b-Catenin is the central mediator of Wnt signaling and is frequently overexpressed in AML in which it is associated with poor prognosis. (haematologica.org)

Inhibition of PP1 leads to enhanced phosphorylation of specific sites on axin by casein kinase I. Axin phosphorylation markedly enhances the binding of glycogen synthase kinase 3, leading to a more active beta-catenin destruction complex. (duke.edu)

Contributing to the modified adherens junctions of the transformed cells are decreased interactions among beta-catenin, E-cadherin, and the actin cytoskeleton. (rupress.org)
The tyrosine-phosphorylated beta-catenin also shows increased detergent solubility, suggesting a decreased association with the actin cytoskeleton. (rupress.org)

β-catenin is a component of the complex cadherin complex whose stabilization is required to activate Wnt/β-catenin signaling. (chemdiv.com)

Dendrites serve critical roles in establishing neuronal circuits and integration of synaptic signals, so mechanisms that regulate their arborization have significant impact on brain function. (jneurosci.org)

Simultaneous loss of erbin and δ-catenin does not enhance severity of this phenotype. (jneurosci.org)

However, whether and how Fam13a regulates alveolar repair/regeneration, especially through modulating metabolism in lung epithelial progenitors remain incompletely understood. (hhs.gov)
AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. (origene.com)

Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/β-catenin signaling. (biomedcentral.com)

All the diversity of catenins forms a complex functional network. (chemdiv.com)
implying that this complex has functional roles that extend beyond its ability to regulate cell adhesion. (jneurosci.org)

However, the molecular mechanisms for APS in regulating SONFH remain unclear. (biomedcentral.com)

These studies identify CK1ε as a critical contributor to activated β-catenin signaling in cancer and suggest it may provide a potential therapeutic target for cancers that harbor active β-catenin. (plos.org)
Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. (chemdiv.com)

2020), Sox17 and β-catenin co-occupy Wnt-responsive en. (xenbase.org)

Two critical oncoproteins, Dnmt1 and β-catenin, mutually regulate one each other's levels and activities in colorectal cancer cells. (nih.gov)
To uncover genetic dependencies in breast cancer cells that harbor active β-catenin signaling, we performed RNAi-based loss-of-function screens in breast cancer cell lines in which we had characterized β-catenin activity. (plos.org)
1 Wnt/b-catenin is also known to drive the emergence and maintenance of leukemia stem cells in AML. (haematologica.org)
regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. (proteopedia.org)

Association between b-catenin and WT1 in myeloid cell lines. (haematologica.org)

The primary structure of beta-catenin consists of an NH2-terminal domain (NDT), a central region represented by 12 Arm-repeats (R1-12), and a COOH-terminal end (CTD). (chemdiv.com)

Keeping beta-catenin at the proper levels appears crucial for the formation of new high-density bone. (smithsonianmag.com)
δ-Catenin-null neurons have no alterations in global levels of active Rac1/RhoA. (jneurosci.org)

However approaches to modulate β-catenin activity for therapeutic purposes have proven elusive to date. (plos.org)

Anatomy10

Diseases6

Chemicals and Drugs44

Analytical, Diagnostic and Therapeutic Techniques and Equipment7

Phenomena and Processes10

Disciplines and Occupations1

Information Science2

Pathway22

CTNNB17

Degradation7

Protein18

Proliferation3

Transcriptional activity1

Morphogenesis3

Accumulates3

Canonical2

Phosphorylation regulates1

Interaction4

Overexpression2

Synergistically2

P1206

Proteins1

Molecule3

Binds1

Embryonic1

Metastasis1

Apoptosis via1

Depletion2

Knockdown1

Tumorigenesis1

Autophagy2

Expression9

Positively1

Nuclear1

Complexes1

Poor prognosis1

Destruction complex1

Actin2

Stabilization1

Neuronal1

Phenotype1

Epithelial2

Axis1

Complex2

Mechanisms1

Cancers2

20201

Cells4

Cell1

Consists1

Levels2

Activity1