Transcriptional activity

Two domains, t1 and t2, exist which affect the GR post-DNA binding transcription activity (37). The major (t1) transactivation domain is 185 amino acid residues ia length with a 58-tesidue a-heUcal functional cote (38). The t1 domain is located at the N terminus of the proteia the minor (t2) trans activation domain residues on the carboxy-terminal side of the DNA binding domain. 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Figure 9.2 Schematic model for transcriptional activation. The TATA box-binding protein, which bends the DNA upon binding to the TATA box, binds to RNA polymerase and a number of associated proteins to form the preinitiation complex. This complex interacts with different specific transcription factors that bind to promoter proximal elements and enhancer elements.

TBP mutants lacking the N-terminal region are fully functional in promoter binding and stimulation of basal transcription and therefore these two functions must be provided by the C-terminal domain. Furthermore, the C-terminal domain of yeast TBP contains all the functions essential for normal yeast cell growth and for responses to specific transcriptional activators with a net negative charge. This C-terminal domain contains two homologous... 

Tjian, R., Maniatis, T. Transcriptional activation a complex puzzle with few easy pieces. Cell 77 5-8, 1994. 

Kaplan, H. B., and Greenberg, E. P. (1987). Overproduction and purification of the luxR gene product transcriptional activator of the Vibrio fischeri luminescence system. Proc. Natl. Acad. Sci. USA 84 6639-6643. 

Androgen receptor Transcriptional regulator Inhibition of androgen receptor transcriptional activity... 

Macromolecules that associate with nuclear receptors to modulate their transcriptional activity. 

CREB stands for cyclic-AMP response element (CRE) binding protein and is a transcription factor. When phosphorylated by cyclic AMP- and cyclic GMP-dependent Protein Kinases or other protein kinases it binds to gene promoters that contain a specific binding site. After binding, the respective transcription activity is modulated. 

ECE isoforms are also involved in the degradation of A 3 peptide. A genetic variant of ECE-1 with an increased transcriptional activity is associated with a decreased risk for AD. Thus, the inhibition of ECE in the CNS may increase the risk for the development of Alzheimer s disease (AD). 

General or basic transcription factors are required for every gene to allow the proper recruitment of RNA polymerases to ensure transcriptional activity. They bind to core promoters in the vicinity of transcriptional start sites in a sequential manner. 

Rel homology domain (RHD) that encompasses a sequence-specific DNA-binding domain, a dimerization domain and a nuclear translocation signal (NLS) (Fig. la). RelA, cRel, and RelB contain a transcription activation domain (TAD). NF-kB 1 and NF-kB2 are synthesized as large precursors, pi 05 and pi 00, that are posttranslationnally processed to generate the mature forms, p50 and p52, which lack a TAD. 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

The N-terminal A/B region whose structure has not yet been defined contains a transcriptional activation function, referred to as activation function 1 (AF-1), which can operate autonomously. The length and sequence of the A/B region in the different NRs are highly variable, revealing a very weak evolutionary... 

The transcriptional activity of NRs is also modulated by various posttranslational modifications of the receptors themselves or of their coregulatory proteins. Phosphorylation, as well as several other types of modification, such as acetylation, SUMOylation, ubiquitinylation, and methylation, has been reported to modulate the functions of NRs, potentially constituting an important cellular integration mechanism. In addition to the modifications of the receptors themselves, such modifications have been reported for their coactivators and corepressors. Therefore, these different modes of regulation reveal an unexpected complexity of the dynamics of NR-mediated transcription. 

---