Genomic analysis of stress response genes

Syngenta Central Toxicology Laboratory, Alderley Park, SK10 4TJ, Cheshire, UK.
Toxicology Letters (Impact Factor: 3.26). 05/2003; 140-141:149-53. DOI: 10.1016/S0378-4274(02)00501-5
Source: PubMed


Mammalian cells respond to a wide range of external stimuli including growth factors, peptide hormones, cytokines, osmotic stress, heat shock, pharmacological agents and toxicants via multiple signalling pathways. Genome-wide transcript profiling simultaneously monitors the gene expression programs downstream of all signal transduction pathways and can identify novel molecular targets for stress-inducing signals. Our laboratory has combined transcript profiling of cytotoxic compounds with experimental systems in which signalling components are disrupted (e.g. small molecule protein kinase inhibitors) to reveal the contribution of specific signalling pathways to the transcriptional response to toxicant-induced stress. A complementary approach for elucidating the molecular mechanisms that regulate transcriptional responses to toxicants involves DNA sequence analysis of gene regulatory regions obtained via data mining of recently completed mammalian genome sequences. Together, these approaches reveal the molecular mechanisms used to finely tune alterations in gene expression, enabling cells to react in an appropriate manner to external stress-inducing stimuli.

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    • "Researchers have subsequently demonstrated that most Hsps have strong cytoprotective effects. They are involved in many regulatory pathways and behave as molecular chaperones for other cellular proteins (Pirkkala et al 2001; Moggs and Orphanides 2003). On the other hand, induction of some other proteins during the stress response results in cell injury. "
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