Stress response activation

Iordanov, M. S. et al. Ribotoxic stress response Activation of the stress-activated protein kinase JNK1 by inhibitors of the peptidyl transferase reaction and by sequence-specific RNA damage to the alpha-sarcin/ricin loop in the 28S rRNA. Mol. Cell. Biol. 17, 3373, 1997. 

PS — non-competitive 80S ribosomal 60S subunit PT, competes with Trichothecin (triggers ribotoxic stress response activating JNK1)... 

Additional roles for Rac and Cdc42 in regulating neutrophil migration appear to be mediated by p21-activated kinases (PAKs), serine/threo-nine protein kinases that are aetivated by Rae and Cdc42 [186]. Activation of PAKs is implicated in aetin remodeling, the stress response, activation of the NADPH oxidase, and initiation of apoptosis. When GTP-bound forms of Rae or Cde42 assoeiate with a characteristic... 

G proteins are molecular amplifiers for a large number of seven-trans-membrane helix receptors that regulate responses like vision, smell and stress response. They are heterotrimeric molecules, Gap, that dissociate into membrane-bound Ga and Gpy signal transmitters upon activation of the receptor. 

The anthrax toxin is a tripartite toxin and consists ofthe binding component protective antigen (PA), the lethal factor (LF), which is a metalloprotease, and the edema factor (EF), which is a calmodulin-dependent adenylyl-cyclase. Both enzyme components are translocated via PA into target cells. PA is activated by furin-induced cleavage and forms heptamers, which are similar to the binding components of C2 toxin and iota toxin. In the low pH compartment of endosomes, the heptamers form pores to allow translocation of LF and EF. LF cleaves six of the seven MEKs (MAPK-kinases) thereby inhibiting these enzymes. The functional consequence is the blockade of the MAPK pathways that control cell proliferation, differentiation, inflammation, stress response, and survival. Whether this is the reason for the LT-induced cell death of macrophages is not clear [1]. 

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. 

The human HS cycle can be considered broadly as a period which leads to the dramatic shift in activities of the transcriptional and translational machinery followed by eventual recovery and resumption of original activities preceding stress. Figure 1 depicts many of the key events in the HS cycle for a typical human cell line such as cervical carcinoma-derived HeLa cells. Most cells respond in an identical fashion, but some cell types that have distinctive HS responses. These differences are manifested by shifts in the relative concentrations of accumulated HS proteins and possibly in the pattern of posttranslational modifications. In all cases, however, the cellular stress response is heralded by induction of a specific transcription factor whose DNA binding activity facilitates increased expression of one or more of the stress-inducible genes. 

Theodorakis, N.G., Zand, D.J., Kotzbauer, P.T., Williams, G.T., Morimoto, R.I. (1989). Hemin induced transcriptional activation of the hsp70 gene during erythroid maturation in K562 cells is due to a heat shock factor mediated stress response. Mol. Cell. Biol. 9,3166-3173. 

A further opportunity for the use of stress-responsive promoters and enhancers is as probes to isolate other stress-responsive genes, the activity of which is not manifest by protein synthesis. As regards the manipulation of stress tolerance as a breeding tool, it is likely that the stress-responsive promoters and enhancers will have a role to play in controlling the expression of adaptive genes when these are transplanted over great evolutionary distances. 

Recent studies have further examined the iron stress response of pseudomonads using an iron-regulated, ice-nucleation gene reporter (inaZ) for induction of the iron stress response (17,18,84). This particular reporter system was developed by Loper and Lindow (85) for study of microbial iron stress on plant surfaces but was later employed in soil assays. In initial. studies, cells of Pseudomonas fluorescens and P. syringae that contained the pvd-inaZ fusion were shown to express iron-responsive ice-nucleation activity in the bean rhizosphere and phyllosphere. Addition of iron to leaves or soil reduced the apparent transcription of the pvd-inaZ reporter gene, as shown by a reduction in the number of ice nuclei produced. 

Changes in the fatty acid profiles of mixed microbial communities may be used in a similar way to detect stress responses or periods of activity. 

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