Stress activated transcription

The problem is that oxidative stress is a necessary part of our response to infection without it, we are unable to mount a genetic defence against pathogens. Oxidative stress activates transcription factors such as NFkB, which coordinate the broader genetic response promoting inflammation and stress resistance.5 Unfortunately, the rise in oxidative stress during ageing also activates NFkB. The pressure to eliminate infection in youth is... 

A second family of MAPKs is referred to as stress-activated protein kinases (SAPKs) [3,14,15]. This includes JNKs, or Jun kinases, named originally for their phosphorylation of the transcription factor c-Jun. SAPKs were first identified in peripheral tissues on the basis of their activation in response to cellular forms of stress, which include X-ray irradiation and osmotic stress. More recently, they have been demonstrated to be activated in brain by several cytokines as well as by synaptic activity [16]. As shown in Figure 23-3, SAPKs are activated by SAPK kinases (SEKs), which are in turn activated by SEK kinases. The Ras-like small G proteins implicated in SEK kinase activation are Rac and Cdc-42. In this case, it appears that Rac/Cdc-42 triggers activation of SEK kinase by stimulating its phosphorylation by still another protein kinase termed p21-activated kinase (PAK). Thus, PAK can be considered a MAPK kinase kinase kinase, which is analogous to the cascade of protein kinases found in yeast (Fig. 23-4). 

How does UV-induced free radical formation activate immune suppression Some have suggested that UV-induced cytokine production is involved. Because both DNA damage and oxidative stress can activate transcription of the cytokines that activate immune suppression,23>24one of the problems faced by investigators in the field was to divorce the effects of DNA damage from membrane oxidation. One approach was to look at the activation of transcription factors in UV-irradiated enucleated cells. Devary and colleagues25 observed that both NF-kB and AP-1 were activated in enucleated... 

M. Jacquet, G. Renault, S. Lallet, J. De Mey, A. Goldbeter, Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in Saccharomyces cerevisiae. J. Cell Biol. 161, 497-505 (2003). 

An important subgroup of MAP kinases has the transcription factor c-Jun as substrate. These kinases are known as c-Jun NH2 terminal kinases (INK) or, due to their activation by stress signals, as stress activated protein kinases (SAPK). The JNK/SAPK proteins are part of their own protein kinase module that conducts stress signals further at the transcription level, and this signaling pathway is therefore known as the JNK/ SAPK pathway. 

C-Jun-N-terminal kinases The JNK/Stress-activated protein kinases (SAPKs) do not respond well to mitogens but are strongly activated by agents that induce cellular stress. These kinases phosphorylate C-Jun transcription factor. The sequence of the tripeptide motif for JNK is Thr-Pro-Tyr. The activators of cytokine and tyrosine kinase receptors transduce signal to the upstream MAPKKKs. These... 

Brown SL, Sekhar KR, Rachakonda G, Sasi S, Freeman ML. 2008. Activating transcription factor 3 is a novel repressor of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)-regulated stress pathway. Cancer Res 68 364-368. 

Table 2.1 Examples of DNA sequence specific transcription factors that regulate stress inducible promoters now being used in therapeutic applications. Shown are the stress inducers, transcriptional activating proteins and consensus response elements recognized by the transacting proteins...

HSF3, identified in chicken, is induced by c-Myb in the absence of cellular stress (Nakai and Morimoto, 1993 Kanei-Ishii et al., 1997). Another isoform of HSF found in human cells, HSF4, possesses transcription represser properties in vivo (Frejtag et al., 2001). Comparisons of HSF protein structure in these organisms indicate the presence of conserved DNA binding domain and three hydrophobic heptad repeats that constitute the trimerization domain. These domains are located within the amino-terminal region of the protein. The stress-responsive transcriptional activation domain is located in the carboxyl-terminal region of the molecule. 

Vanadium compounds are also believed to interact with cellular stress pathways that lead to apoptosis [70], as shown in Figure 11.3. One way vanadium compounds can influence these processes is by catalyzing the formation of intracellular ROS and NOS. All of the phosphorylation/dephosphorylation reactions eventually activate transcription factors that move to the nucleus to initiate the DNA breakdown characteristic of apoptosis. Vanadium is postulated to interfere with the dephosphorylation of some of these proteins by inhibition of various protein phosphatases. The... 

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