Search results for TCF3

Showing 19 results out of 23

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Protein (4 results from a total of 4)

Identifier: R-HSA-3209896
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: TCF3: P15923
Identifier: R-HSA-3209894
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: TCF3: P15923
Identifier: R-HSA-5228649
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: TCF7L1: Q9HCS4
Identifier: R-HSA-5689542
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: TFPT: P0C1Z6

Interactor (2 results from a total of 2)

Identifier: P15923-3
Species: Homo sapiens
Primary external reference: UniProt: P15923-3
Identifier: P15923-1
Species: Homo sapiens
Primary external reference: UniProt: P15923-1

Set (3 results from a total of 3)

Identifier: R-HSA-8956528
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8951530
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8951427
Species: Homo sapiens
Compartment: nucleoplasm

Reaction (4 results from a total of 8)

Identifier: R-HSA-6801213
Species: Homo sapiens
Compartment: nucleoplasm, mitochondrial intermembrane space
Binding of TP53 (p53) to the p53 response element in the second intron of the TRIAP1 (TP53-regulated inhibitor of apoptosis, also known as p53 survival factor or p53CSV) gene induces TRIAP1 transcription (Park and Nakamura 2005). Recently, TRIAP1 has been characterized as a gene-specific repressor of p21 (CDKN1A). TRIAP1 knockdown leads to augmented p21 expression before and during p53 activation and thus slows down cell proliferation (Andrysik et al. 2013).
Identifier: R-HSA-8951428
Species: Homo sapiens
Compartment: nucleoplasm
RUNX3 forms a ternary complex with beta-catenin (CTNNB1) and its binding partner TCF7L2 (TCF4). In addition to TCF7L2, RUNX3 is also able to interact with LEF1, TCF7L1 (TCF3) and TCF7 (also known as TCF1). The interaction involves the Runt domain of RUNX3 and the HMG box of TCF7L2 (Ito et al. 2008).
Identifier: R-HSA-8956568
Species: Homo sapiens
Compartment: nucleoplasm
RUNX1, in complex with CBFB, binds to the core TAL1 complex consisting of TAL1 (SCL), TCF3 (E2A) or TCF12 (HEB), LMO1 or LMO2, LDB1 and GATA1, GATA2 or GATA3 (Wilson et al. 2010, Tijssen et al. 2011, Sanda et al. 2012, Mansour et al. 2014, Hoang et al. 2016). Assembly of the RUNX1- and GATA3-containing TAL1 complex is positively regulated by the CDK7-containing CAK complex (Kwiatkowski et al. 2014).
Identifier: R-HSA-4411357
Species: Homo sapiens
Compartment: nucleoplasm
TCF7L1 (also known as TCF3), TCF7L3 (also known as LEF1) and TCF7L2 (also known as TCF4) have been demonstrated to bind to the MYC gene in vivo and in vitro and to mediate beta-catenin dependent transcription (Park et al, 2009; He et al, 1998; Sierra et al, 2006). Aberrant beta-catenin dependent activation of the MYC gene contributes to oncogenic signaling and cellular proliferation in colorectal and other cancers (see for instance Sansom et al, 2007; Moumen et al, 2013; reviewed in Wilkins and Sansom, 2008; Cairo et al, 2012).
Binding of RUNX3 to the CTNNB1:TCF7L2 and possibly to the CTNNB1:LEF1 and TCF7L1 complexes, prevents binding of CTNNB1 complexes to the MYC promoter, thus negatively regulating MYC transcription (Ito et al. 2008).

Complex (3 results from a total of 3)

Identifier: R-HSA-8951528
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8951429
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-8951432
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (2 results from a total of 2)

Identifier: R-HSA-201722
Species: Homo sapiens
Compartment: nucleoplasm
Once in the nucleus, beta-catenin is recruited to WNT target genes through interaction with TCF/LEF transcription factors. This family, which consists of TCF7 (also known as TCF1), TCF7L1 (also known as TCF3), TCF7L2 (also known as TCF4) and TCF7L3 (also known as LEF1), are HMG-containing transcription factors that bind to the WNT responsive elements in target gene promoters (reviewed in Brantjes et al, 2002). In the absence of WNT signal, TCF/LEF proteins recruit Groucho/TLE repressors to inhibit transcription; upon WNT stimulation, beta-catenin can displace Groucho/TLE from TCF/LEF proteins to initiate transcriptional activation (reviewed in Chen and Courey, 2000). Although this model for WNT-dependent activation of target genes is widely accepted, it is important to note that TCF/LEF proteins are not redundant and can contribute to WNT target gene expression in a number of different ways (reviewed in Brantjes et al, 2002; MacDonald et al, 2009). In particular, TCF7L1 (TCF3) is thought to have a more pronounced repressor function than other TCF/LEF family members. A couple of recent studies in Xenopus and mammalian cells show that WNT- and beta-catenin-dependent phosphorylation of TCF7L1(TCF3) promotes its dissociation from the promoter of target genes and allows gene expression through relief of this repression activity (Hikasa et al, 2010; Hikasa et al, 2011).


The role of beta-catenin at WNT promoters hinges upon its ability to act as a scaffold for the recruitment of other proteins. The structure of beta-catenin consists of 12 imperfect ARM repeats (R1-12) flanked by an N-terminal and C-terminal extension (NTD and CTD respectively), with a conserved Helix C located between R12 and the CTD. Nuclear beta-catenin interacts with TCF/LEF at WNT target genes through ARM domains 3-9 (Graham et al, 2000; Poy et al, 2001; Xing et al, 2008). The N and the C terminal regions are important for the recruitment of transcriptional activator and repressors that contribute to WNT target gene expression (reviewed in Mosimann et al, 2009; Valenta et al, 2012). The N-terminal ARM domains 1-4 recruit the WNT-pathway specific activators BCL9:PYGO while the C-terminal region (R11-CTD) interacts with a wide range of general transcriptional activators that are involved in chromatin remodelling and transcription initiation. These include HATs such as P300, CBP and TIP60, histone methyltransferases such as MLL1 and 2, SWI/SNF factors BRG1 and ISWI and components of the PAF complex (reviewed in Mosimann et al, 2009; Valenta et al, 2012). Although many binding partners have been identified for the C-terminal region of beta-catenin, in many cases the timing and relationship of these interactions and indeed, the exact complex composition remains to be elucidated. Moreover, because many of the interacting partners appear to bind to overlapping regions of beta-catenin, it is unlikely that they all bind simultaneously. For simplicity, the interactions have been depicted as though they occur independently of one another; more accurately they are likely to cycle successively on and off beta-catenin to promote an active chromatin structure (reviewed in Willert and Jones, 2006; Valenta et al, 2012).
Identifier: R-HSA-9013508
Species: Homo sapiens
In the nucleus, NICD3 forms a complex with RBPJ (CBF1, CSL) and MAML (mastermind) proteins MAML1, MAML2 or MAML3 (possibly also MAMLD1). NICD3:RBPJ:MAML complex, also known as the NOTCH3 coactivator complex, activates transcription from RBPJ-binding promoter elements (Lin et al. 2002). While NOTCH1 prefers paired RBPJ binding sites, NOTCH3 preferentially binds to single RBPJ binding sites (Ong et al. 2006).


NOTCH3 coactivator complex induces transcription of the well established NOTCH target genes HES1 (Lin et al. 2002, Boelens et al. 2014), HEYL (Maier and Gessler 2000, Geimer Le Lay et al. 2014), HES5 (Lin te al. 2002, Shimizu et al. 2002), and HEY2 (Wang et al. 2002).

NOTCH3 positively regulates transcription of the pre-T-cell receptor alpha chain (PTCRA, commonly known as pT-alpha or pre-TCRalpha) (Talora et al. 2003, Bellavia et al. 2007). IK1, splicing isoform of the transcription factor Ikaros (IKZF1), competes with RBPJ for binding to the PTCRA promoter and inhibits PTCRA transcription. NOTCH3, through pre-TCR signaling, stimulates expression of the RNA binding protein HuD, which promotes splicing of IKZF1 into dominant negative isoforms. These dominant negative isoforms of IKZF1 heterodimerize with IK1, preventing its binding to target DNA sequences and thus contributing to sustained transcription of PTCRA (Bellavia et al. 2007, reviewed by Bellavia, Mecarrozzi, Campese, Grazioli, Gulino and Screpanti 2007).

NOTCH3-triggered pre-TCR-signaling downregulates the activity of the transcription factor TCF3 (E2A), through ERK-dependent induction of ID1. Inhibition of TCF3-mediated transcription downstream of NOTCH3 contributes to development of T-cell lymphomas in transgenic mice expressing NICD3 (Talora et al. 2003). Activation of ERKs downstream of NOTCH3-stimulated pre-TCR signaling leads to phosphorylation of the transcription factor TAL1, formation of the TAL1:SP1 complex, and activation of cyclin D1 (CCND1) transcription, which stimulates cell division (Talora et al. 2006).

NOTCH3 signaling can activate NF-kappaB (NFKB)-mediate transcription either indirectly, through activation of pre-TCR signaling, or directly, through association of NOTCH3 with IKKA. NFKB is constitutively active in T lymphoma cells derived from NOTCH3 transgenic mice (Vacca et al. 2006).

Transcription of the PLXND1 gene, encoding the semaphorin receptor Plexin D1, is directly stimulated by NOTCH1 and NOTCH3 coactivator complexes. PLXND1 is involved in neuronal migration and cancer cell invasiveness (Rehman et al. 2016). Expression of FABP7 (BLBP) in radial glia is positively regulated by NOTCH1 and NOTCH3 during neuronal migration (Anthony et al. 2005, Keilani and Sugaya 2008).


NOTCH3 gene is frequently amplified in ovarian cancer (Park et al. 2006). NOTCH3 coactivator complex directly stimulates DLGAP5 transcription. DLGAP5 is involved in G2/M transition and is overexpressed in ovarian cancer cells. (Chen et al. 2012). Another gene overexpressed in ovarian cancer whose transcription is directly stimulated by NOTCH3 is PBX1 (Park et al. 2008). The NOTCH3 coactivator complex directly stimulates WWC1 gene transcription. WWC1 gene encodes protein Kibra, involved in Hippo signaling. NOTCH3-mediated induction of WWC1 positively regulates Hippo signaling and inhibits epithelial-to-mesenchymal transition (EMT) in triple negative breast cancer cells (Zhang et al. 2016).

Icon (1 results from a total of 1)

TCF

Species: Homo sapiens
Curator: Karen Rothfels
Designer: Cristoffer Sevilla
TCF icon
Generic representation of a T-cell Factor
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