Transcription factor Tcf

A FIGURE 14-23 Induction of gene transcription by activated MAP kinase, in the cytosoi, MAP kinase phosphoryiates and activates the kinase p90 , which then moves into the nucieus and phosphoryiates the SRF transcription factor. After transiocating into the nucieus, MAP kinase directiy phosphoryiates the transcription factor TCF Together, these phosphoryiation events stimuiate transcription of genes (e.g., c-fos) that contain an SRE sequence in their promoter. See the text for detaiis. [See R. Marais et al., 1993, Ce//73 381, and V. M. Rivera et al., 1993, Mot Cell Blot 13 6260.]... 

Activation of MAP kinase following stimulation of a growth factor receptor leads to phosphorylation and activation of two transcription factors, TCF and SRF. These associate into a tiimerlc complex that promotes transcription of various early-response genes (see Figure 14-23). 

In line with expression of A3 adenosine receptors in cells and tissues like mast cells, spleen and thymus putative binding sites for a number of transcription factors relevant for protein expression in inflammation and infection were identified in the promoter region of the A3 receptor gene (Atkinson et al. 1997 Zhao et al. 1999). These include activator protein 1 (AP-1) which regulates gene expression in response to viral and bacterial infections or to stimulation by cytokines. Additional binding sites for transcription factors with specificity for immune cells are for the T cell-specific T cell factor F-2-a (TcF-2-a) and for the B cell-specific E2aECB. 

Frizzled receptor is an example of receptors activated by the Wnt ligand. Upon activation of the Frizzled receptor, the protein kinase activity of GSK3/I is inhibited, and />-catenin is stabilized and translocates to the nucleus, where it associates with the transcription factors of the TCF family. It is not known how the activated Frizzled receptor inhibits the protein kinase activity ofGSK3/I. The protein Disshelved is involved in this downregulation. 

Fig. 5. Schematic representation of RA and Wnt3a on the Cdxl promoter. Wnt 3a interacts with surface frizzled receptors, resulting in a cascade of events in the cytosol, leading to stabilization of /fcatcnin. /1-catenin then translocates to the nucleus, where it presumably interacts with LEF/TCF transcription factors resident on two LREs on the Cdxl promoter, inducing Cdxl expression. RA interacts with the RAR moiety of RXR-RAR heterodimers, and regulates Cdxl through an RARE situated 5 to the transcriptional start site, as indicated.

VI. Tcf/p-Catenin Complexes Bipartite Transcription Factors Involved in Wingless/Wnt Signaling... 

Tcf-1 and Lef-1 are not classical transcription factors in that they are incapable of activating transcription of reporter gene constructs from a synthetic enhancer containing multimerized Tcf/Lef binding sites. Lef-1 acts as... 

VI. Tcf/p-CATENIN COMPLEXES BIPARTITE TRANSCRIPTION FACTORS INVOLVED IN WINGLESS/Wnt SIGNALING... 

Cooperative binding by NFAT and API occurs only when their weak binding sites are located at a precise distance, quite close to each other In DNA. Recent studies have shown that the requirements for cooperative binding are not so stringent in the case of some other transcription factors and control regions. For example, the EGR 1 control region contains a composite binding site to which the SRF and TCF... 

Wingless and other Wnt signals act through two cell-surface proteins, the receptor Frizzled and coreceptor Lrp, and an intracellular complex containing p-catenin (see Figure 15-32). Wnt signaling promotes the stability and nuclear localization of p-catenin, which either directly or indirectly promotes activation of the TCF transcription factor. 

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