The Stress Response and Stress Proteins
John J. Lemasters, Constance Oliver in Cell Biology of Trauma, 2020
The stress response, or heat shock response, is a fundamental molecular mechanism with which organisms compensate for environmentally induced perturbations of cellular function. Heat and a variety of other stresses induce a suite of stress or heat shock proteins. These proteins play diverse cellular roles in minimizing or repairing damage due to stress, or in inducing tolerance to subsequent stress. Even in the absence of stress, these proteins or their close relatives are essential for a variety of cellular processes. Due to the vital nature of stress protein function and the importance of their induction as a model for gene regulation, interest in the stress response has undergone explosive growth, averaging more than 800 publications in the primary literature per year during the past five years. More than 500 publications examine the relationships between the stress response and the other subjects in this volume (e.g., reactive oxygen species, ischemia-reperfusion injury, inflammation). Accordingly, here we can but touch upon a limited number of aspects of the stress response that are relevant to the cell biology of trauma, and so can provide only a general introduction to the field. We will, however, cite many of the excellent recent reviews that provide entree to the primary literature.
Heat Shock Proteins and Cell Thermotolerance
Leopold J. Anghileri, Jacques Robert in Hyperthermia In Cancer Treatment, 2019
In human cells, the existence of such a protein whose activation would correspond to the first step in the heat-shock response is suggested by the work of Kao and Nevins.96,97 Induction of HSP by viral infection has been reported by several authors. Newcastle disease virus,98 herpes simplex virus,100 and simian virus 40 and Polyomavirus99 each induce an increased synthesis of at least the HSP70. Nevins96 demonstrated that upon adenovirus infection of HeLa cells, the HSP response was not due to a general stress response to the infection, but rather was the result of the specific action of the viral E1A gene product. By analogy with the known role of the E1A protein in the induction of the early viral mRNAs, they suggested that the viral protein was not a direct activator of transcription, but instead its action was indirect and involved its interaction with a protein factor of the host cell. The possibility that this factor is the same as that involved in the heat induction of HSP is further suggested by the observation (unpublished, reported in Reference 97) that some cells which support early viral transcription in the absence of E1A function also show a high level of heat-shock gene expression in the absence of hyperthermic treatment.
Caenorhabditis elegans Aging is Associated with a Decline in Proteostasis
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
The proteostasis network is defined as the total complement of cellular factors that are required to maintain proteostasis, or more specifically, to maintain a healthy balance between protein synthesis, folding, and degradation to ensure a healthy proteome. In the category of protein folding regulators, molecular chaperones play a crucial role in that the heat shock response (HSR) and the unfolded protein response (UPR) protect cells from heat-induced protein damage [69,70]. The HSR is mediated by the transcription factor heat shock factor 1 (HSF1), which triggers a rapid increase in the transcription and translation of molecular chaperones. In parallel, global translation rates decline, allowing the heat-shocked cells to switch away from protein synthesis and toward protein refolding or degradation [71]. While we typically think about the molecular chaperones acting under conditions of acute proteotoxic stress, they also have a housekeeping function in that HSF1 [72,73], UPR signaling components [74–76], and some heat-inducible molecular chaperones are actually encoded by essential genes that function early in development, rendering mutants embryonic lethal. As such, these stress-inducible pathways must be required to maintain proteostasis under normal conditions as well as conditions of acute stress.
High altitude hypoxia on brain ultrastructure of rats and Hsp70 expression changes
Published in British Journal of Neurosurgery, 2019
Wen-Hua Li, Yu-Xiang Li, Jun Ren
Heat shock response is a kind of cellular level biological response to stress. Since heat shock response was found by Tissiéres et al.1 in the study on Drosophila larvae in 1974; heat shock response has become a hot research topic in various fields. The product of heat shock response was heat shock protein (HSP), while the first gene to be cloned and identified was HSP70. The human HSP70 gene is located in chromosome 1, 5, 6, 9, 11 and 14; and also considered to be present in chromosome 21.2,3 Their common code of a set of relative molecular mass from 66,000 to 78,000 was highly related to the protein. HSP70 gene family members can be used as a molecular chaperone to promote the correct folding, assembly and transport of new synthetic proteins, and promote the re-folding or degradation of proteins4,5. HSP70 protein plays an important protective role in the formation of heat tolerance or poison tolerance, as well as the prevention of oxidative damage. Heat stress protein is very important for the stability and adaptability of the intracellular environment. It is known that nucleotide substitution, deletion or insertion mutations can adjust the start of function or transcriptional activity6, while different HSP70 expression levels can modulate stress, or disease susceptibility or tolerance.7 Therefore, this study aimed to observe changes in brain tissue and HSP70 expression in high-altitude hypoxia rats, in order to clarify the mechanism of HSP70 in high-altitude hypoxia adaptation.
zHSF1 modulates zper2 expression in zebrafish embryos
Published in Chronobiology International, 2018
Lucas Mennetrier, Tatiana Lopez, Benoist Pruvot, Nadhir Yousfi, Olivier Armant, Hanae Hazhaz, Vincent Lhuissiez, Carmen Garrido, Johanna Chluba
The reaction to temperature changes is regulated by the heat shock response (HSR) that protects cells from damage due to various stressors, including heat. The key factor of the HSR is the transcription factor HSF1. In response to stress, HSF1 trimerizes and activates transcription of heat shock (HS) protein genes and other stress-related genes (Fujimoto and Nakai 2010; Pirkkala et al. 2001). Indeed, the implication of HSF1 in circadian systems was demonstrated in vitro and in vivo by the transcriptional control of the clock gene Period 2 (Per2) (Reinke et al. 2008; Buhr et al. 2010; Tamaru et al. 2011). HSF1 binding regions or elements (HSEs) were found in the upstream region of the Per2 gene in mammals (Kornmann et al. 2007; Reinke et al. 2008; Tamaru et al. 2011).
Design, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Man Yang, Chenyao Li, Yajing Li, Chen Cheng, Meiyun Shi, Lei Yin, Hongyu Xue, Yajun Liu
HSP90 consists of three domains: the N-terminus, C-terminus, and the middle domain15,16. Classical HSP90 inhibitors competitively bind to the ATP binding pocket at the N-terminus. Over twenty HSP90 N-terminal inhibitors have entered clinical trials for the treatment of a variety of cancers17,18. Allosteric binding sites are also found at the C-terminus and the middle domain. HSP90 C-terminal inhibitors have been extensively studied in recent years because they do not cause a rescue cascade known as the heat shock response, which is often observed in the modulation of HSP90 with N-terminal inhibitors19,20. Many natural products and synthetic small molecules have been identified as HSP90 C-terminal inhibitors; however, they have not yet entered clinical trials for cancer therapy21.
Related Knowledge Centers
- Cellular Stress Response
- Gene Expression
- Oxidative Stress
- Protein
- Protein Folding
- Chaperone
- Proteostasis
- Heat Shock Protein
- Proteinopathy
- Intracellular Space