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IndraLab
Statements
reach
"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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"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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"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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"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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"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)."
"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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"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."
sparser
"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."
"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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"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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"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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"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."
"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"