All organisms must deploy stress-defence systems with more or less specific tasks to cope with disturbances and restore normal physiological conditions after disturbance. These mechanisms are found in any cell and several systems are conserved throughout life, from prokaryotes to eukar-yotes. The widespread occurrence of stress-defence mechanisms indicates that already very early in the evolution of life the defence against disturbances was a crucial problem to solve. Stress defence is thus closely linked to the idea of homeostasis, the tendency to regulate the internal state at a level independent from the changeable environment. Some systems that evolved in the early days of life have maintained their tasks mostly unchanged throughout evolution. We have already glimpsed some stress-defence systems in Chapter 5, when discussing the issue of longevity. It was noted then that upregulated stress defence in the wide sense is one of the most obvious signatures of a long life. In this section we will discuss the various stress-defence systems in more detail.
Korsloot et al. (2004) reviewed the cellular stress-defence responses with an emphasis on arthropods. In the book, the authors distinguished five different systems: (i) basal signal transduction systems, (ii) stress proteins, (iii) the oxidative stress response, (iv) metallothionein and associated systems, and (v) mixed-function oxygenase. It was also noted that there are many crosslinks between the different stress-defence systems. These crosslinks help to coordinate the cellular response, which is needed to maintain integrity. In addition, many genes of the stress-defence system have promoters responding to more than one challenge. For example, the metallothionein promoter has metal-responsive elements enabling induction by metal stress, but it also has antioxidant-responsive elements and steroid hormone receptor-binding sites. Korsloot et al. (2004) even went one step further and argued that the different systems cooperate as a single, integrated, cellular stress-defence system. In the course of this chapter, we will meet genomic evidence that this may indeed be the case. However, before presenting the genome-wide profiling studies we will shortly discuss the five best-investigated systems separately. Later sections will show that these five are by no means the only stress-responsive systems in the cell, but they serve to illustrate the most important principles of how stress-induced gene expression is brought about.
A theme common to all stress-induced gene expression is that stress signals converge on the activation of transcription factors, which bind to specific DNA sequences in the promoters of stress-induced genes. More generally these factors are called trans-acting factors and the DNA sequences to which they bind are cis-regulatory elements. It is of considerable interest to know which sequences may act as transcription factor-binding sites and which genes have promoters with these sequences. Screening of the 5' region of a gene and identification of potential binding sites for transcription factors can help considerably to understand the biochemical context and the function of a gene. Conversely, when groups of genes are up- or downregulated in concert, and the same transcription factor-binding site appears in their promoters, this may indicate that they are regulated by the same transcription factor. One can never be sure, however, that a certain sequence, even if it conforms to a cis-regulatory element consensus sequence, is acting as a transcription factor-binding site in vivo, because transcriptional regulation is an extremely complicated process and is very much context-dependent (Wray et al. 2003). TRANSFAC® is a database on eukaryotic transcription factors, their genomic binding sites, and their DNA-binding profiles (www.gene-regulation.com/pub/databases.html). An overview of consensus sequences of transcription factor-binding sites appearing in this chapter is given in Table 6.1.
The scientific literature on cellular stress covers an extensive territory of biochemistry. It would be a hopeless task to try and cover all this ground here; instead we aim to present those aspects of stress-defence mechanisms that we think are necessary to understand the genomic studies on stress responses in an ecological context. We pay special attention to the pathways by which stress is translated into gene expression.
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