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"By bioinformatics analyses, we discovered that the promoter regions of all RAS genes contained putative T-cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites, and beta-catenin induced the binding of LEF-1 to these sites in kidney tubular cells."

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"Moreover, CK1 dependent phosphorylation in contrast to CK2 disrupts the association of beta-catenin and LEF-1 but does not impair DNA binding of LEF-1."

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"Most importantly, the nuclear accumulation of beta-catenin activated T-cell factor and lymphocyte enhancer factor-1 (TCF-1 and LEF-1), which acts as a transcriptional activator."

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"Both VDR and 1,25 (OH) 2 D suppress beta-catenin stimulated LEF1 and TCF driven reporter activity."

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"Since LEF1 is strongly induced by Wnt and beta-catenin in Ewing sarcoma cells we speculate that this might lead to sequestration of EWS and ETS proteins by LEF1 and inhibition of EWS and ETS dependent transcription."

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"Then activated β-catenin in turn activates downstream transcriptional factors, T-cell factor (TCF) and lymphoid enhancer factor (LEF) to further regulate the targeted genes [ xref , xref ]."

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"This naturally occurring Lef-1 transcript was used in order to eliminate the effect of beta-catenin activating Lef-1."

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"In these clusters we observed the expression of cell survival and cell cycle genes CCND2, NFKB1, PLK1, NAIP; putative oncogenes JUNB, TOX, AHI1; novel cancer testis genes GTSF1, SYCP1 as well as embryonic stem cell genes TCF3, EVA1, CHD1; genes promoting inflammatory T cell signaling ITK, LCK, FYB, GNLY, CCL18, CCL26, E-Selectin; skin homing chemokine receptor CCR4; cytokines (and their cognate receptors) that were reported to be secreted by the Th17 cells IL-26, IL-17A, IL-17F, IL-21 and IL-21R; the IL-22 cytokine; actin binding protein PLS3; matrix metalloproteinase MMP12; downstream positive regulator of WNT and beta-catenin signalling LEF1; transcription factors STAT5A, MXI and POU2AF; markers of T cell activation TFRC, IRF4; and other signaling genes including T3JAM, FOSL1, SHD1A, SERPINB4 (XREF_FIG, XREF_FIG and XREF_SUPPLEMENTARY)."

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"Down-regulation of β-catenin by β-catenin shRNA reduced LEF-1 promoter activity (Fig. 10e), whereas overexpression of β-catenin enhanced LEF-1 promoter activity (Fig. 10f)."

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"Beta-Catenin does not bind to the DNA but directs TCF and LEF1 to regulate the genes responsible for cell proliferation."

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"Here, we show that Hypoxia Inducible Factor-1alpha (HIF-1alpha), a principal mediator of hypoxic adaptations, modulates Wnt and beta-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of downstream effectors LEF-1 and TCF-1."

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"74 Ectopic expression of activated Akt did not appear to activate beta-catenin signaling in the cells examined as measured by changes in the levels of accumulation of cytosolic beta-catenin activation of LEF1 dependent transcription."

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"This result strongly suggests that the most conserved (by position and sequence similarity among five mammalian species) and proximal (relative to the TSS) Lef1 and Tcf binding site ' c ' is the functionally most important of the three Lef1 and Tcf binding sites for Lef1 mediated activation of the murine Dkk3 gene by Wnt1 and beta-catenin signaling."

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"We observed that G-17 not only enhanced the expression of total cellular beta-catenin, but also increased nuclear beta-catenin accumulation and beta-catenin-dependent LEF-1 activity."

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"As noted previously [11], beta-catenin strongly enhances binding of LEF-1 to chromatin templates, and CK2 enhanced this effect."

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"Furthermore, GRIP1 and beta-catenin can synergistically enhance the activity of both AR and Lef1, and both coactivators are recruited specifically to AR driven and Lef1 driven promoters."

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"In situ hybridization experiments for the Wnt and beta-catenin targets lef1 and ctnnb2 revealed that lef1 and ctnnb2 are expressed in deposited interneuromast cells at 2 dpf (XREF_FIG, arrowheads)."

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"In reporter gene assays using the pGL3OT reporter containing LEF responsive elements, beta-catenin enhanced LEF1 activity, and coexpression of beta-catenin and DBC1 further enhanced LEF1 function in a synergistic manner (XREF_FIG)."

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"Wnt3a signaling transiently stabilizes beta-catenin, allowing it to bind nuclear LEF-1 and TCF DNA binding proteins and activate target genes."

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"β‐catenin can activate lymphoid enhancing factor‐1 (LEF‐1) at the transcription level."

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"The binding of canonical Wnt proteins to members of the Frizzled receptors (Fzd) and its co-receptors results in the activation of Dishevelled and inhibition of the beta-catenin degradation complex, allowing targeting of T-cell specific transcription factor and lymphoid enhancer binding factor 1 (TCF/LEF) family of transcription factors and transcriptional activation of Wnt target genes XREF_BIBR, XREF_BIBR."

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"Recently, for endometrial cancer similar observations have been described confirming promoter binding sites for the Wnt and beta-catenin inducing transcription factor LEF-1 and, interestingly, also for the EMT inducing transcription factors SNAI1 and SNAI2 XREF_BIBR."

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"Consistent with the model in which beta-catenin acetylation enhances its binding to LEF1 and leads to increased chromatin occupancy of LEF1 by stabilizing LEF1, beta, and catenin complex, XREF_BIBR, XREF_BIBR our results further showed that DBC1 enhances the interaction of beta-catenin with LEF1 (XREF_FIG) and is required for efficient recruitment of LEF1 and beta-catenin to their target chromatin regions (XREF_FIG), probably through protecting beta-catenin from SIRT1 mediated deacetylation (XREF_FIG)."

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"In fact, a balance of stimulation and suppression of genes by HNF4alpha is influenced by the beta-catenin activated transcription factor LEF1 to establish zonal specific expression of various enzymes (e.g. glutamine synthetase)."

"Upon wnt activation, cytoplasmic beta-catenin is stabilized and enters the nucleus, where it associates with transcription factors, notably tcf (t cell factor) and lef (lymphoid enhancer-binding factor), to regulate the transcription of target genes. Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as lef-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus."

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"Thus, beta-catenin accumulates, enters the nucleus and activates genes acting as a co-activator of the transcription factors belonging to the T cell factor and lymphoid enhancer factor-1 (TCF and LEF1) family [XREF_BIBR]."

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"After Wnt binds to cell-surface receptors Fzd and Lrp, beta-catenin is stabilized in the cytoplasm and translocated to the nucleus where it activates the Tcf and Lef1 transcription complex to regulate the promoter activity of Wnt signaling target genes [XREF_BIBR, XREF_BIBR]."

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"Moreover, we demonstrate that activation of beta-catenin and Lef -1 signaling by Wnt-1 or by overexpression of beta-catenin itself is inhibited by caveolin-1 expression."

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"These findings indicate that beta-catenin alone can mediate the nuclear import of lef-1 through the direct binding."

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"It has been reported to target the mRNA of Lef1, the transcription factor that is upregulated by beta-catenin [XREF_BIBR]."

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"The up-regulation of Wnt1 expression and activation of the WNT1 and beta-catenin signaling pathway in the adult VM, however, might contribute at least in part to the increased proliferation of locally[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Wnt3a signaling transiently stabilizes beta-catenin, allowing it to bind nuclear LEF-1 and TCF DNA binding proteins and activate target genes (Cadigan and Waterman, 2012)."

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"Mazumdar et al., have demonstrated that Hif1a modulates Wnt and beta-catenin signaling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of the downstream effectors Lef-1 and Tcf-1."

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"Here, we show that Hypoxia Inducible Factor-1α (HIF-1α), a principal mediator of hypoxic adaptations, modulates Wnt/β-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing β-catenin activation and expression of downstream effectors LEF-1 and TCF-1."

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"Therefore, binding of beta-catenin to different interaction partners in the nucleus may direct both TCF and LEF1 dependent and -independent transcriptional regulation."

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"Because scales develop in an invariant sequence we were also able to analyze expression of conserved Wnt and beta-catenin targets lef1 and axin2 in fixed specimens."

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"In the stem cell niche, Wnt signaling and beta-catenin stabilization are considered to activate the Lef1 and T-cell factor complex, which binds to its target genes and promotes stem cell activation and proliferation; these constitute critical steps required to support hair growth."

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"WNT signalling culminates in the accumulation of β-catenin, which activates the T cell factor (TCF)–lymphoid enhancer factor (LEF) transcription factor complex that induces the expression of target genes such as MYC ."

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"Thus, Wnt signaling increases cytoplasmic levels of beta-catenin, which enters the nucleus and interacts with other factors to activate a TCF and LEF1 mediated transcriptional program 5."

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"Beta-Catenin stabilizes cell-cell junctions by anchoring cell adhesion molecules (i.e., Cadherins) in the actin cytoskeleton, activates the LEF1 and TCF family of transcription factors, and is involved in the amplification and separation of centrosomes [XREF_BIBR]."

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"CEMP1-p4 stimulation upregulated the expression of beta-catenin and glycogen synthase kinase 3 beta (GSK-3B) and activated the transcription factors TCF1/7 and Lymphoid Enhancer binding Factor 1 (LEF1) at the mRNA and protein levels."

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"Ectopic overexpression of beta-catenin in 293 cells also induced the assembly of the beta, catenin, and LEF-1 complex and activated gene transcription from a LEF-1-dependent promotor."

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"Consequently, ERG overexpression increased active beta-catenin level in the cells and enhanced TCF and LEF1 luciferase reporter activity, which could be partially blocked by WNT-3A inhibitor IWP-2."

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"In proximal tubular cells, constitutively activated beta-catenin promotes the binding of LEF-1 to these sites, and overexpression of beta-catenin or various Wnt ligands induces expression of multiple RAS genes (XREF_FIG) [XREF_BIBR]."

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"It has been shown that in chick neural cells, phosphorylation of beta-catenin at tyrosine 489 (Y489) targets it to the nucleus where it binds to its partner (s) TCF and Lef1 and acts as a co-activator of transcription XREF_BIBR."

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"Furthermore, co-expression of beta-catenin and DBC1 synergistically enhanced LEF1 activity."

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"Tcf7l1 forms a complex with beta-catenin and thereby loses chromatin occupancy in mouse embryonic stem cells and breast cancer cells XREF_BIBR, whereas recombinant beta-catenin strongly promotes binding of Lef1 to chromatin templates in vitro XREF_BIBR."

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"We show with antisense β-catenin oligonucleotides that up-regulated LEF1 is not activated by β-catenin in palate EMT."

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"TGF-β signaling can directly increase LEF1 expression through SMADs and inhibit glycogen synthase kinase 3β (GSK-3β) through the phosphoinositide 3-kinase (PI3K)–Akt pathway, which enables β-catenin–dependent activation of LEF-1 to induce EMT ( xref , xref )."

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"Of note, β-catenin binds to Lef1 and activates Lef1 transcription complex, leading to down-regulation of E -cadherin expression [ xref ]."

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"As a result, the beta-catenin is accumulated in the cytoplasm and translocated to the nucleus where it interacts with and activates TCF and Lef1 transcription complex initiating Wnt activated gene expression [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

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"The other negative regulator SOX17 repress the β-catenin dependent spatial and temporal LEF-1 activation [ xref ]."

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"PITX2 isoforms regulate the LEF-1 promoter, and beta-catenin synergistically enhanced activation of the LEF-1 promoter in combination with PITX2 and Lef-1 isoforms."

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"69 Finally, HIF1alpha itself modulates Wnt and beta-catenin signaling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of the downstream effectors LEF-1 and TCF-1."

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"The results of ChIP showed that overexpression of β-catenin increased the binding of LEF-1 to the LINC01278 promoter (Fig. 3A)."

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"To specifically target cells that activate the Wnt and beta-catenin pathway in the lesion site, we generated a TetActivator line using regulatory elements of the direct Wnt and beta-catenin target lef1 (lef1 : TetA AmCyan; Supplementary Fig. 4b)."

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"Degradation of phosphorylated β-catenin limits β-catenin nuclear translocation to inactivate LEF1 translation, resulting in an inhibited Wnt/β-catenin signaling activation."

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"In fact, a balance of stimulation and suppression of genes by HNF4α is influenced by the β-catenin activated transcription factor LEF1 to establish zonal specific expression of various enzymes (e.g. glutamine synthetase)."

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"Reporter assays revealed that ectopic expression of Sox17 suppresses Wnt3A and beta-catenin activation of the Lef-1 promoter in cell lines."

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"These experiments demonstrated that 1 h of laminar FSS (10 dynes/cm 2)-induced translocation of beta-catenin from the cytoplasm to the nucleus and activated an LEF-1 and TCF reporter gene."

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"These results demonstrate that forced expression of Dvl-1 elevates NANOG expression, probably due to the accumulation of β-catenin, which can activate the Lef1."

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"Next, we looked at the possibility that normal palates are not using β-catenin–activated LEF1 to transform the MEE to mesenchyme."

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"In this study, DACT2 decreased the expression of active β-catenin and its downstream genes in NPC cells and suppressed the activity of the β-catenin/LEF1 complex."

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"Ten genes (CCND1, JUN, CCND2, EGFR, LEF1, MET, MMP7, MYC, TCF3, TERT, and beta-catenin itself (CTNNB1)) were up-regulated by beta-catenin and two (FOS and CDH1) were down-regulated; for the remaining genes, the directionality of the beta-catenin effect was not reported."

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"Thus far, the only major signaling pathway that has been consistently been shown to be directly involved in transformation of epithelium to mesenchyme is β-catenin/lymphoid-enhancing factor 1 (LEF1; xref ; xref ), but whether or not β-catenin will activate LEF1 depends on specific isoforms of LEF/TCF transcription factor that contain an alternative COOH-terminal “E” tail ( xref )."

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"Thus far, the only major signaling pathway that has been consistently been shown to be directly involved in transformation of epithelium to mesenchyme is beta-catenin and lymphoid-enhancing factor 1, but whether or not beta-catenin will activate LEF1 depends on specific isoforms of LEF and TCF transcription factor that contain an alternative COOH-terminal " E " tail."

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"The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and beta-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter."

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"CTNNB1 activates Lef1 transcription and upregulates Lef1 promoter activity in vitro."

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"Beta-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells."

"Phosphorylated lrp5/6 leads to inhibition of the so-called beta-catenin destruction complex (which includes axin, gsk3, dvl, ck1, and the tumor suppressor adenomatous polyposis coli), resulting in the stabilization and translocation of beta-catenin in the nucleus, where it activates target genes through binding to tcf/lef transcription factors."

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"Lymphoid enhance factor1 (Lef1) is a transcriptional regulator of the Wnt and beta-catenin signaling cascade and is activated by nuclear beta-catenin."

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"However, the authors reported that tyrosine phosphorylation of beta-catenin does not change its binding affinity to LEF-1 nor enhances cyclin D1 transactivation, a nuclear target of beta-catenin and L[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"RAS genes contain putative T cell factor (TCF)/lymphoid enhancer factor (LEF)-binding sites in their promoter regions, and beta-catenin induces the binding of LEF-1 to these sites in kidney tubular cells."

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"Here, we show that hypoxia inducible factor-1alpha (HIF-1alpha), a principal mediator of hypoxic adaptations, modulates Wnt and beta-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing beta-catenin activation and expression of the downstream effectors LEF-1 and TCF-1."

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"We performed in situ hybridization with the Wnt and beta-catenin target lef1 and a dgfp probe for a transgenic Wnt and beta-catenin reporter line, Tg (Tcf and Lef-miniP : dGFP) that contains 6 copies of a consensus TCF/Lef binding site followed by destabilized EGFP."

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"ChIP experiments also confirmed the endogenous binding of the transcription factor LEF-1 to the LINC01278 promoter, and showed that β-catenin can enhance the binding of LEF-1 to the LINC01278 promoter."

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"Here, we show that hypoxia inducible factor-1α (HIF-1α), a principal mediator of hypoxic adaptations, modulates Wnt/β-catenin signalling in hypoxic embryonic stem (ES) cells by enhancing β-catenin activation and expression of the downstream effectors LEF-1 and TCF-1."

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"These authors additionally demonstrated that Wt1 knockout resulted in an epicardium specific reduction in beta-catenin, with down-regulation of the Wnt / beta-catenin target Lef1 [XREF_BIBR]."

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"Expression analysis of a selection of these transcripts demonstrates a similar profile, suggesting interaction and or co-regulation of Wnt and beta-catenin antagonists, Wnt and beta-catenin target element TCF4, and EMT related transcription factors SNAI2 and LEF1, which can be activated by both Wnt and beta-catenin and TGF-beta signalling (XREF_FIG) XREF_BIBR."

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"The LEF1 gene is aberrantly transcribed in colon cancers because promoter 1 (P1) is a Wnt target gene and is activated by TCF–β-catenin complexes."

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"For instance, PIASy directs the Wnt and beta-catenin mediator LEF1 to PML nuclear bodies, which results in repression of LEF1 activity."

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"Relationships between hypoxia and Wnt signaling have been explored in neural stem cells where HIF-1alpha enhances beta-catenin activation and expression of downstream effectors LEF-1 and TCF-1 XREF_BIBR."

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"It also showed that betacatenin relieves Tcf3 repression of Lef1, and subsequently activate Wnt target genes through its interaction with Lef1."

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"Cotransfection of beta-catenin and LEF-1 into Chinese hamster ovary cells induced transactivation of a LEF-1 reporter, which was blocked by the N-cadherin-derived molecules."

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"We hypothesize that endothelial cells are responsive to Wnt signals and that Lef1, a member of the vertebrate specific Wnt and beta-catenin throughput inducing transcription factors ' sub-family Lef1 and Tcf1, mediates this responsiveness and promotes endothelial cell invasion."

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"In the uninfected parental cell lines, stable expression full length LEF1 (variant 1) led to beta-catenin activation of an LEF1 responsive luciferase reporter."

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"Genetic mutations or altered protein expression of beta-catenin and Apc have been implicated in human cancers, and all result in increased beta-catenin levels, which in turn lead to increased Lef-1 and Tcf-1 transcriptional activity and deregulated proliferation [XREF_BIBR]."

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"We show with antisense beta-catenin oligonucleotides that up-regulated LEF1 is not activated by beta-catenin in palate EMT."

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"We provide evidence that DDIP suppresses Lef-1 luciferase reporter activity stimulated by Wnt1, Dvl2 or beta-catenin, interacts with the TCF4, beta, and catenin complex, and disrupts the interaction of TCF4 and beta-catenin by promoting TCF4 degradation through the proteasome pathway."

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"The c-myc gene has been identified as a direct target of LEF-1 and TCF proteins, which are repressed by wild-type APC and activated by beta-catenin in colon cancer cells [XREF_BIBR]."

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"Thus, miR-26b is a tumor repressor that is a potent inhibitor of colon cancer cell proliferation that blocks Wnt and beta-catenin dependent activation of LEF-1 and a model for tumor suppressor like activity of miR-26b is illustrated in XREF_FIG."

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"We have shown previously that promoter 1 of the LEF1 gene is activated by T cell factor (TCF)-beta-catenin complexes in transient transfection assays, suggesting that LEF1 is a target of the Wnt pathway in colon cancer."

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"However, Wnt5a and Wnt4, which neither elevate the level of cytosolic beta-catenin nor activate LEF1 dependent transcriptional activity (Shimizu et al., 1997), did not increase ALP activity in C3H10T1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter."

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"Importantly, the beta-catenin targets LEF-1 and CD44 remained expressed at elevated levels and ectopically throughout the crypt-villus axis in triple mutant mice, indicating that ablation of YAP and T[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Considering the wide-spread and successful use of beta-catenin to activate the LEF1 transcription factor, one might ask why use Smads instead?"

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"Also, for the first time we present evidence that TGFbeta 3 up-regulates LEF1 mRNA and that Smads, not beta-catenin, activate LEF1 in this embryonic EMT."

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"In the nucleus, β-catenin binds and activates the lymphoid enhancer factor (LEF)/T cell factor (TCF) transcription factor to regulate the expression of Wnt target genes ( xref )."

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"The elimination of Wnt and beta-catenin signaling in either Lef1 or Wnt10b knockout mice resulted in down-regulation of Shh expression."

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"TCF-7 and LEF-1 transcription factors, which are represented by V$LEF1TCF1_Q4, can be activated by β-catenin and are involved in canonical WNT-signaling (Brade et al., xref ; Chen et al., xref ; Pal and Khanna, xref ; Kwon et al., xref ; Naito et al., xref )."

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"This result is somewhat consistent with the findings that Wnt and beta-catenin pathways induce the 2.5 kb Lef-1 promoter in cell lines (Filali et al, 2002) and that Shh-knockout mice lack Wnt5a mRNA i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"There are putative TCF/LEF binding sites in the RAS promoter region through bioinformatics analyses, and β-catenin could trigger LEF-1 to bind to these sites in renal tubular cells (Zhou et al., 2015b)."

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"We show with antisense beta-catenin oligonucleotides that up-regulated LEF1 is not activated by beta-catenin in palate EMT."

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"TCF-7 and LEF-1 transcription factors, which are represented by V$ LEF1TCF1_Q4, can be activated by beta-catenin and are involved in canonical WNT signaling."

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"This naturally occurring Lef-1 transcript was used in order to eliminate the effect of β-catenin activating Lef-1."

"Activated dvl binds and inhibits the phosphorylation of beta catenin by gsk3beta/alfa, blocking beta catenin degradation), so that beta catenin accumulates and translocates to the nucleus, where it interacts with the t cell specific factor (tcf)/lymphoid enhancer binding factor 1 (lef-1) transcription factor and induces the transcription of target genes such as c-jun, c-myc, and cyclin d1"