TBL1-related protein 1 (TBLR1/TBL1XR1) and Transducing β-like protein 1 (TBL1X/TBL1) were originally identified as subunits of the co-repressor silencing mediator for retinoic and thyroid hormone receptor (SMRT) and nuclear receptor co-repressor (NCoR) complexes. These two factors are required for the exchange of co-repressor complexes for co-activators by acting as adaptors to recruit the ubiquitin/proteasome machinery that degrades the co-repressor proteins during ligand mediated activation of transcription. Co-factor exchange driven by TBLR1/TBL1XR1 and TBL1X/TBL1 appears to be the mechanism by which c-Jun and NF-κB mediated transcription is activated and is therefore likely to be the mechanism employed by other signal-dependent transcription factors as well. In addition, both TBLR1/TBL1XR1 and TBL1X/TBL1 have essential roles in regulating the Wnt-signaling pathway by recruiting β-catenin to Wnt target genes to activate transcription. Depletion of TBLR1/TBL1XR1 significantly inhibited Wnt-beta-catenin- induced gene expression and oncogenic growth in vitro and in vivo. Research studies have shown that upregulation of TBLR1/TBL1XR1 is observed in a variety of solid tumors, and is correlated with advanced tumor stage, metastasis and poor prognosis.
This gene is a member of a conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of numerous developmental processes. In mouse, the ortholog of this gene is expressed in the cerebral cortex, hippocampus, amygdala and olfactory bulb and is thought to play an important role in neuronal migration and axonal projection. In mouse, the C-terminal region of this protein was found to be necessary and sufficient for association with the guanylate kinase domain of calcium/calmodulin-dependent serine protein kinase.
This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human ortholog of mouse Tbx21/Tbet gene. Studies in mouse show that Tbx21 protein is a Th1 cell-specific transcription factor that controls the expression of the hallmark Th1 cytokine, interferon-gamma (IFNG). Expression of the human ortholog also correlates with IFNG expression in Th1 and natural killer cells, suggesting a role for this gene in initiating Th1 lineage development from naive Th precursor cells.
Transcription factor 4 (TCF4), also known as SEF2, ITF2, E2-2, and ME2, binds to the immunoglobulin enchancer Mu-E5/KE5-motif. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Binds to the E-box present in the somatostatin receptor 2 initiator element (SSTR2-INR) to activate transcription By similarity. Human TCF4 mRNA expression is particularly high in the brain. Usage of numerous 5' exons of the human TCF4 gene potentially yields in TCF4 protein isoforms with 18 different N-termini. In addition, the diversity of isoforms is increased by alternative splicing of several internal exons. Some isoforms contain a bipartite nuclear localization signal and are exclusively nuclear, whereas distribution of other isoforms relies on heterodimerization partners. TCF4 preferentially binds to either 5'-ACANNTGT-3' or 5'-CCANNTGG-3'.TCF4 has several splicing isoforms that are expressed differentially in tissues and during cancer progression. The scopel of molecular weight of several isoforms is about 60-90 kDa.
2 series of isoforms, L and S, are produced by use of alternative promoter usage. Additional isoforms seem to exist,Transcriptional activator involved in T-cell lymphocyte differentiation. Necessary for the survival of CD4(+) CD8(+) immature thymocytes. Isoforms lacking the N-terminal CTNNB1 binding domain cannot fulfill this role. Binds to the T-lymphocyte-specific enhancer element (5'-WWCAAAG-3') found in the promoter of the CD3E gene. May also act as feedback transcriptional repressor of CTNNB1 and TCF7L2 target genes. TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by TCF7 and CTNNB1.,induction:By TCF7L2 and CTNNB1.,sequence caution:Wrong choice of frame.,similarity:Belongs to the TCF/LEF family.,similarity:Contains 1 HMG box DNA-binding domain.,subunit:Binds the armadillo repeat of CTNNB1 and forms a stable complex. Interacts with AES, TLE1, TLE2, TLE3 and TLE4.,tissue specificity:Predominantly in T-cells. Also detected in proliferating intestinal epithelial cells and in the basal epithelial cells of mammary gland epithelium.
Enhances the phosphorylation and activation of AKT1, AKT2 and AKT3. Promotes nuclear translocation of AKT1. Enhances cell proliferation, stabilizes mitochondrial membrane potential and promotes cell survival.
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