Activation of Transcription

In addition to PXR and CAR, other NRs are also involved in the regulation of CYP3A expression. For example, activation of the GR by dexamethasone increases the expression of both PXR and CAR through glucocorticoid response elements (GREs) in their promoters, and this can increase the expression of CYP3AS S6. The transcription factor hepatocyte nuclear factor-4 (HNF- 

4) seems to play an important role in CYP3A expression as well. It has been shown that binding of HNF-4 to the promoter of CYP3A23 is necessary to maintain both its constitutive expression 

Mouse models have also been used to demonstrate a role for PXR in regulating the levels of toxic bile acids. It had been previously established 

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Steitz has suggested that DNA bending by CAP could contribute to activation of transcription by looping the DNA around CAP to provide for contacts between RNA polymerase and DNA upstream of the CAP-binding site. Such a model could explain how CAP can activate transcription from a variety of distances from the RNA polymerase-binding site since the size of the loop could vary. 

Once the TLRs have bound their respective ligand they initiate a signalling cascade to alert the host to the presence of a threat. This signal begins with specific adapter proteins and leads to the activation of transcription factors such as NFkB, ERF-3 and IRF-7 as shown in Fig. 1. These activated transcription factors cause changes in gene expression typically leading to the production of cytokines. 

Activation of transcription by the binding of a transcription factor to a DNA-regulatory sequence. 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

Ikeda K, Nagano K, Kawakami K (1993) Possible imphcations of Spl-induced bending of DNA on synergistic activation of transcription. Gene 136(l-2) 341-343 Ishida T, Hamano A, Koiwa T, Watanabe T (2006) 5 long terminal repeat (LTR)-selective methy-lation of latently infected HIV-1 provirus that is demethylated by reactivation signals. Retrovirology 3 69... 

A bacterial two-hybrid system has been developed that, similar to the yeast system, functions via activation of transcription (Dove and Hochschild, 1998 Joung et al., 2000). RNA polymerase (RNAP) in E. coli consists of an enzymatic core composed of the a, (3, and (3 subunits in the stoichiometry a2(3(3, and one of several c factors that enable the enzyme to recognize specific promoters (Heilman and Chamberlin, 1988). Many bacterial transcriptional activator proteins bind the promoters they regulate and interact directly with subunits of RNAP. The most commonly observed contact is between activator proteins and the a subunit of RNAP (Ebright and Busby, 1995). The function of the a subunit is to initiate the assembly of RNAP by forming a dimer (Igarashi et al., 1991). 

Arnica montana L. (Arnica) has been used for treating bruises and swelling in Western medicine on account of its ability to elaborate sesquiterpene lactones, such as hele-nalin and dihydrohelenalin, which are thought to inhibit the activation of transcription factor nuclear factor (NF)-kB, which is responsible for the transcription of genes involved in encoding mediators for the inflammatory process. 

Gilmour, P.S. et al. (1997) Free radical activity of industrial fibers role of iron in oxidative stress and activation of transcription factors. Environmental Health Perspectives, 105, 1313-1317. 

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