Inducers, transcription and

Hypoxia (3 % O2) in primary cultures of human pulmonary fibroblasts and pulmonary vascular smooth muscle cells induced transcription and translation of IL-6 (4- to 5-fold) in both cell types (Tamm et al. 1998). Hyperoxia-induced expression of IL-6 was suppressed by 50 % to 60 % in the presence of platelet-activating factor antagonist WEB2170, or neutrahsing anti-platelet-derived growth factor antibodies. 

More recently, no interference of up to 2 mM Cd " with a protein-based Ca " sensor yellow chameleon, YC3.60 was observed. The authors concluded from their study that Ca is not necessary for Cd " (1-30 pM)-induced transcription and that as cells succumb to metal toxicity, Ca " is released [547]. Further studies would be required to confirm these observations and to finally resolve the role of Ca in Cd -induced stress and cell death signaling pathways. 

Cyclosporine A (CsA) is a water-insoluble cyclic peptide from a fungus composed of 11 amino acids. CsA binds to its cytosolic receptor cyclophilin. The CsA/cyclophilin complex reduces the activity of the protein phosphatase calcineurin. Inhibition of this enzyme activity interrupts antigen receptor-induced activation and translocation of the transcription factor NEAT to the nucleus which is essential for the induction of cytokine synthesis in T-lymphocytes. 

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. 

When considering the role of phosphorylation in the regulation of the HS response, it is indeed curious that oxidative stress and heat induce a protein tyrosine phosphatase at the transcriptional level (Keyse and Emslie, 1992). Whether this phosphatase has any role in the regulation of HSF phosphorylation is not known, but it does indicate that both transcriptional and translational regulation of signaling... 

Kroes, R.A., Abravaya, K., Seidenfeld, J., Morimoto, R.l. (1991). Selective activation of human heat shock gene transcription by nitrosurea antitumor drugs mediated by isocyanate-induced damage and activation of heat shock transcription factor. Proc. Natl. Acad. Sci. USA 88,4825-4829. 

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