High-level, heat-regulated synthesis of proteins in eukaryotic cells

Dréano, Michel; Brochot, Jean; Myers, André; Cheng-Meyer, Cecilia; Rungger, Duri; Voellmy, Richard; Bromley, Peter

doi:10.1016/0378-1119(86)90380-x

Cited by 71 publications

(28 citation statements)

References 25 publications

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“…However, no studies on the effects of SV on HSF1 transactivation using reporter constructs have been described. To accurately measure the effects of SV on this HSF1 function, we have stably transfected L929 cells with the p2500-CAT construct (LHSECAT cells), in which high level CAT gene expression is controlled by the human HSP70 promoter (36). Dose-dependent inhibition by SV of heat shockinduced CAT expression in the LHSECAT cells can be seen in Fig.…”

Section: The Phosphatase Inhibitor Sodium Vanadate Decreases Stressmentioning

confidence: 99%

“…Instead, we propose that the mechanism by which heat shock controls GR transactivation requires HSF1 activity. In the p2500-CAT reporter used in this study, expression of chloramphenicol acetyltransferase (CAT) is controlled by the human HSP70 promoter containing consensus heat shock elements (HSEs) known to be activated by the binding of heat shock factor (36). The pMMTV-CAT plasmid contains the complete mouse mammary tumor virus-long terminal repeat promoter (MMTV-LTR) upstream of CAT (37).…”

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confidence: 99%

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Heat and Chemical Shock Potentiation of Glucocorticoid Receptor Transactivation Requires Heat Shock Factor (HSF) Activity

Periyasamy

Jones

et al. 2000

Journal of Biological Chemistry

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Heat shock and other forms of stress increase glucocorticoid receptor (GR) activity in cells, suggesting cross-talk between the heat shock and GR signal pathways. An unresolved question concerning this cross-talk is whether heat shock factor (HSF1) activity is required for this response. We addressed this issue by modulating HSF1 activity with compounds acting by distinct mechanisms: sodium vanadate (SV), an inhibitor of protein phosphatases; and wortmannin, an inhibitor of DNA-dependent protein kinase. Using HSF1-and GR-responsive CAT reporters, we demonstrate that SV inhibits both HSF1 activity and the stress potentiation of GR, while having no effect on the hormone-free GR or HSF1. Paradoxically, SV increased hormone-induced GR activity in the absence of stress. In contrast, wortmannin increased HSF1 activity in stressed cells and had no effect on HSF1 in the absence of stress. Using the pMMTV-CAT reporter containing the negative regulatory element 1 site for DNA-dependent protein kinase, wortmannin was found to increase the GR response. However, in cells expressing a minimal promoter lacking negative regulatory element 1 sites, wortmannin had no effect on the GR in the absence of stress but increased the stress potentiation of GR. Our results show that the mechanism by which GR activity is increased in stressed cells requires intrinsic HSF1 activity. The glucocorticoid receptor (GR)1 is a member of the nuclear receptor family of proteins that act as hormone-activated transcription factors (1, 2). Since the GR is known to be involved in the organismal response to stress (3), and since the hormonefree GR is known to reside in the cytoplasm as a complex containing heat shock proteins (HSPs) (4), we and others have investigated the role of the heat shock response in controlling GR function. Early evidence to suggest a relationship between these responses includes the ability of heat shock or chemical stress (arsenite) to cause nuclear translocation of hormone-free GR in mouse L929 and Chinese hamster ovary cells (5, 6) and a partial increase in GR-mediated gene expression in Chinese hamster ovary cells subjected to heat or chemical shock in the absence of hormone (6). Heat shock-induced nuclear translocation of hormone-free GR has also been documented in the liver of rats subjected to whole-body hyperthermia (7, 8) as well as in COS cells expressing human GR (9). Evidence to suggest that heat shock-induced nuclear translocation of hormone-free GR can result in altered expression of endogenous genes has also been accumulating. For example, heat shock treatment of COS and Hela cells in the absence of hormone results in GR-mediated transrepression of the collagenase promoter (9), while heat shock treatment of murine macrophages results in a pattern of Fc receptor expression or repression that is identical to that observed in response to hormone (10). More recently, heat shock-induced translocation of hormone-free GR has been implicated in the process of stress-induced apoptosis in leukemic cells (11).In the presenc...

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Section: The Phosphatase Inhibitor Sodium Vanadate Decreases Stressmentioning

confidence: 99%

mentioning

confidence: 99%

Heat and Chemical Shock Potentiation of Glucocorticoid Receptor Transactivation Requires Heat Shock Factor (HSF) Activity

Periyasamy

Jones

et al. 2000

Journal of Biological Chemistry

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“…The hsp7OB gene (59) encoding yet another member of the hsp70 family of proteins is entirely silent in nonstressed cells but highly active in stressed cells. Experiments with reporter genes driven by the promoter of this gene showed a 500-to 1,200-fold differential between expression levels in heat-shocked and unheated cells (16). It follows from these considerations that the activities of regulatory factors (HSF being the only factor of this kind known to date) involved in the control of these genes must be tightly regulated.…”

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confidence: 96%

Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1.

Baler¹,

Dahl²,

Voellmy³

1993

Mol. Cell. Biol.

435

354

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Transcriptional activity of heat shock (hsp) genes is controlled by a heat-activated, group-specific transcription factor(s) recognizing arrays of inverted repeats of the element NGAAN. To date genes for two human factors, HSF1 and HSF2, have been isolated. To define their properties as well as the changes they undergo during heat stress activation, we prepared polyclonal antibodies to these factors. Using these tools, we have shown that human HeLa cells constitutively synthesize HSF1, but we were unable to detect HSF2. In unstressed cells HSF1 is present mainly in complexes with an apparent molecular mass of about 200 kDa, unable to bind to DNA. Heat treatment induces a shift in the apparent molecular mass of HSF1 to about 700 kDa, concomitant with the acquisition of DNA-binding ability. Cross-linking activation of transcription of hsp genes is indeed mediated by denatured proteins (4), suggesting protein denaturation as the common denominator of many of the disparate treatments inducing the response. Earlier studies have also suggested that hsp gene expression may be subject to autoregulation (15). In concordance with findings that members of the hsp7O family of proteins are capable of binding to denatured proteins and peptides (18,36,38), as well as of associating with nascent polypeptides (8), several recent studies showing down-regulation of the transcriptional stress response following overexpression of hsp7O (52) and the propensity of hsp7O to directly bind HSF (2, 7) have implicated hsp70 as the autoregulatory factor. After the cloning of HSF genes from a variety of organisms (13, 41, 43-45, 51, 63), support for a negative mode of regulation of HSF activity has come from observations of constitutive transcriptional activity of mutated Saccharomyces cerevisiae HSF (9, 35) and of constitutive DNA-binding activity of wild-type Drosophila and human HSF expressed in bacteria (13,41,45). Further evidence for such a regulatory mechanism has been provided by experiments showing that derepression of DNA-binding activity of human HSF can be reproduced in vitro by treatment with heat (33; see reference 13 for analogous experiments with Drosophila cells) and with agents affecting protein conformation (34). Surprisingly, considering the divergence of transcriptional mechanisms, quite analogous findings concerning the role of denatured proteins in triggering the stress response (21) and its autoregulation by hsp7O (DnaK) and other hsps (20,(53)(54)(55)(56) were made with bacteria.The second question with which this study is mainly concerned is directed toward the biochemical analysis of molecular events occurring when HSF is converted from an

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“…The heat shock promoters, especially the hsp70 promoters, have been used often in gene therapy strategies because they are both heat inducible and efficient in initiating and regulating transcription of therapeutic genes (50). The promoter of one of the inducible heat shock protein systems, HSP70, can activate gene expression several thousand-fold in response to hyperthermia (51). The minimal hsp70 promoter is almost exclusively sensitive to temperature, and it was suggested several years ago to use the hsp70 promoter and local hyperthermia could be used to control transgene expression (3).…”

Section: Applications Of Local Temperature Elevation In Gene Therapymentioning

confidence: 99%

Spatio-Temporal Control of Gene Expression and Cancer Treatment Using Magnetic Resonance Imaging–Guided Focused Ultrasound

Moonen

2007

Clinical Cancer Research

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Local temperature elevation may be used for tumor ablation, gene expression, drug activation, and gene and/or drug delivery. High-intensity focused ultrasound (HIFU) is the only clinically viable technology that can be used to achieve a local temperature increase deep inside the human body in a noninvasive way. Magnetic resonance imaging (MRI) guidance of the procedure allows in situ target definition and identification of nearby healthy tissue to be spared. In addition, MRI can be used to provide continuous temperature mapping during HIFU for spatial and temporal control of the heating procedure and prediction of the final lesion based on the received thermal dose. The primary purpose of the development of MRI-guided HIFU was to achieve safe noninvasive tissue ablation.The technique has been tested extensively in preclinical studies and is now accepted in the clinic for ablation of uterine fibroids. MRI-guided HIFU for ablation shows conceptual similarities with radiation therapy. However, thermal damage generally shows threshold-like behavior, with necrosis above the critical thermal dose and full recovery below. MRI-guided HIFU is being clinically evaluated in the cancer field.The technology also shows great promise for a variety of advanced therapeutic methods, such as gene therapy. MR-guided HIFU, together with the use of a temperature-sensitive promoter, provides local, physical, and spatiotemporal control of transgene expression. Specially designed contrast agents, together with the combined use of MRI and ultrasound, may be used for local gene and drug delivery.

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High-level, heat-regulated synthesis of proteins in eukaryotic cells

Cited by 71 publications

References 25 publications

Heat and Chemical Shock Potentiation of Glucocorticoid Receptor Transactivation Requires Heat Shock Factor (HSF) Activity

Heat and Chemical Shock Potentiation of Glucocorticoid Receptor Transactivation Requires Heat Shock Factor (HSF) Activity

Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1.

Spatio-Temporal Control of Gene Expression and Cancer Treatment Using Magnetic Resonance Imaging–Guided Focused Ultrasound

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