Transcription-induced stress

Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14, R546-551 Pfaffle P, Gerlach V, Bunzel L, Jackson V (1990) In vitro evidence that transcription-induced stress causes nucleosome dissolution and regeneration. J Biol Chem 265 16830-16840 Poch O, Winsor B (1997) Who s who among the Saccharomyces cerevisiae actin-related proteins ... 

The enhanced expression of metal-induced stress proteins is controlled primarily at the transcriptional level similar to the induction of hsps by heat (Wu et al. 1986). Regulation of hsp genes in eukaryotic systems is mediated by a cw-acting heat shock control element (HSE) that is found in multiple copies upstream of the transcriptional start site (Pelham 1982). Transcriptional activation of the hsp genes is mediated by a ran -acting protein, known as the heat shock factor (HSF), which binds specifically to the HSE (Wu 1984a,b). 

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. 

As mentioned above, many transcription factors are not always active. Rather the activity of transcription factors is often achieved by induced reversible modification. Most frequently is the addition of phosphate groups (phosphorylation) to Ser, Thr, or Tyr residues. For the AP-1 component c-Jun the phosphorylation at Ser63 and Ser73 enhances activity when cells are subjected to stress, e.g. radiation. Phosphorylation is, however, dispensable for c-Jun-dqDendent tissue homeostasis in the liver, indicating that certain activities do not require the regulatory enhancement. Jun-N-teiminal kinase and a kinase called RSK or p38 catalyze the phosphorylation of AP-1. 

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... 

As more is learned about the chromosomal effects on HS gene expression, it is important to point out that these genes are actually a subset of inducible responses to cellular stress. Not all of these inducible responses involve HSF, and this indicates that cells have diversified transcriptional responses to cope with different types of stress. This diversification is manifested by glucose regulated genes (grp), as well as the metallothionein and oxidant-injury genes (Watswich, 1988 Storz et al., 1990 Devary et al., 1992 Skroch et al., 1993 Xu, 1993). 

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