Is TCF4 a Wnt target gene?
WNT Signaling in Health and Disease The DNA binding protein TCF7L2 (TCF4) has dual roles in WNT-dependent signaling as both positive and negative transcriptional regulator—functions that are dependent on the presence of isoform-specific protein domains that mediate interactions with various regulatory proteins.
What is TCF Wnt pathway?
T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors are the major end point mediators of Wnt/Wingless signaling throughout metazoans. TCF/LEFs are multifunctional proteins that use their sequence-specific DNA-binding and context-dependent interactions to specify which genes will be regulated by Wnts.
What type of cells produce a Wnt signal?
The stem cells in the IFE niche are also Wnt-producing cells (figure 1c, inset). RNA in situ hybridization experiments have shown that the same stem cell expresses both Axin2 and Wnt4 or Wnt10 [9].
What are Wnt target genes?
We define “direct Wnt targets” as genes whose regulatory DNA can be physically associated with T-cell factors (TCFs) or other transcription factors (TFs) and whose expression is modulated by the recruitment of β-catenin to regulatory chromatin by these TFs.
What genes does B catenin activate?
In the nucleus β-catenin activates transcription of Wnt/β-catenin-target genes such as c-myc and cyclinD1 (Maretzky et al, 2005; Reiss et al, 2005).
What is the TCF in cell?
The TCF/LEF family (T cell factor/lymphoid enhancer factor family) is a group of genes that encode transcription factors which bind to DNA through a SOX-like high mobility group domain.
What is TCF beta catenin?
TCF-β-catenin nuclear complexes have been reported to oscillate with the cell cycle, suggesting potential nuclear roles independent of DNA association (Ding et al., 2014). Further, β-catenin is reported to play an essential, non-transcriptional role in self-renewal of mouse epiblast stem cells (Kim et al., 2013).
Where is the WNT pathway located?
Wnt signaling plays a critical role in embryonic development. It operates in both vertebrates and invertebrates, including humans, frogs, zebrafish, C. elegans, Drosophila and others. It was first found in the segment polarity of Drosophila, where it helps to establish anterior and posterior polarities.
Where does Wnt come from?
The term “Wnt” is derived from the terms wingless and int. The Int oncogenes, including Int1, were first identified in the mouse mammary tumor. In 1987, investigators sequenced wingless in Drosophila and found it was the homolog of int-1. Thus, the int/Wingless family became the Wnt family and int1 became Wnt1.
How do you activate Wnt protein?
To activate Wnt signaling, one can add Wnt protein, either in a purified form or as conditioned medium to cells. Cells producing active Wnt can be obtained from the ATCC (see also the reagents page). Active Wnt protein can be obtained from several companies.
What is beta-catenin used for?
β-catenin is part of a protein complex that form adherens junctions. These cell–cell adhesion complexes are necessary for the creation and maintenance of epithelial cell layers and barriers. As a component of the complex, β-catenin can regulate cell growth and adhesion between cells.
Is APC a tumor suppressor gene?
The APC protein acts as a tumor suppressor, which means that it keeps cells from growing and dividing too fast or in an uncontrolled way. It helps control how often a cell divides, how it attaches to other cells within a tissue, and whether a cell moves within or away from a tissue.
What is Wnt in a cell?
Wnt proteins are secreted glycoproteins that activate different intracellular signal transduction pathways. They regulate cell proliferation and are required for proper embryonic development. Misregulation of Wnt signaling can result in various diseases including cancer.
What happens when Wnt pathway is activated?
Cell migration Convergent extension is further regulated by the Wnt/calcium pathway, which blocks convergent extension when activated. Wnt signaling also induces cell migration in later stages of development through the control of the migration behavior of neuroblasts, neural crest cells, myocytes, and tracheal cells.
What is the function of TCF4 In Wnt?
T cell factor 4 (TCF4), also known as TCF7L2, represents a key transcription factor that mediates canonical Wnt signaling, which plays a central role in embryonic development and in the maintenance of tissue homeostasis (6–8).
Does TCF4 bind to β-catenin?
TCF4 is a binding partner of β-catenin, as both mediate the effects of canonical Wnt signaling. Notably, overexpression of mutated β-catenin (S33Y), which activates TCFs but cannot be inactivated, caused a >10-fold higher increase in reporter activity in wild-type SW837 cells (TOP/FOP: 34.3) than in wild-type HT-29 cells (TOP/FOP: 2.9; P< 0.001).
Is TCF4 expression associated with chemoradioresistance in primary rectal cancer?
TCF4 expression correlates with chemoradioresistance in primary rectal cancers and in CRC cell lines Gene expression profiling of primary rectal cancers showed that the Wnt transcription factor TCF4was significantly overexpressed in those tumors that were resistant to preoperative 5-FU-based chemoradiotherapy (5).
Does vitamin D affect the Wnt/β-catenin signaling pathway in colon cancer?
As this pathway is involved in the proliferation of numerous cell types, it seems likely that vitamin D may act to inhibit the Wnt/β-catenin signaling pathway in other cancer cell types as well. Munoz and colleagues have explored the role of vitamin D and many additional target genes that are controlled by this hormone in colorectal cancer. 280–284