Invited Review: Interplay between molecular chaperones and signaling pathways in survival of heat shock

2002 ◽  
Vol 92 (4) ◽  
pp. 1743-1748 ◽  
Author(s):  
Vladimir L. Gabai ◽  
Michael Y. Sherman
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Signaling Pathways ◽  
Molecular Chaperones ◽  
Mammalian Cells ◽  
Survival Pathways ◽  
Extracellular Signal ◽  
A Cell ◽  
Stress Kinase ◽  
Nonapoptotic Cell Death

Heat shock of mammalian cells causes protein damage and activates a number of signaling pathways. Some of these pathways enhance the ability of cells to survive heat shock, e.g., induction of molecular chaperones [heat shock protein (HSP) HSP72 and HSP27], activation of the protein kinases extracellular signal-regulated kinase and Akt, and phosphorylation of HSP27. On the other hand, heat shock can activate a stress kinase, c-Jun NH2-terminal kinase, thus triggering both apoptotic and nonapoptotic cell death programs. Recent data indicate that kinases activated by heat shock can regulate synthesis and functioning of the molecular chaperones, and these chaperones modulate activity of the cell death and survival pathways. Therefore, the overall balance of the pathways and their interplay determine whether a cell exposed to heat shock will die or survive and become stress tolerant.

Chaperoning signaling pathways: molecular chaperones as stress-sensing`heat shock' proteins

2002 ◽  
Vol 115 (14) ◽  
pp. 2809-2816 ◽  
Author(s):  
Ellen A. A. Nollen ◽  
Richard I. Morimoto
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Signaling Pathways ◽  
Molecular Chaperones ◽  
Growth Control ◽  
Normal Function ◽  
Stress Sensing ◽  
As Stress ◽  
Shock Proteins

Heat shock proteins interact with multiple key components of signaling pathways that regulate growth and development. The molecular relationships between heat shock proteins, various signaling proteins and partner proteins appear to be critical for the normal function of signal transduction pathways. The relative levels of these proteins may be important, as too little or too much Hsp70 or Hsp90 can result in aberrant growth control, developmental malformations and cell death. Although the functions of heat shock proteins as molecular chaperones have been well characterized, their complementary role as a `stress-induced' proteins to monitor changes and alter the biochemical environment of the cell remains elusive. Genetic and molecular interactions between heat shock proteins, their co-chaperones and components of signaling pathways suggest that crosstalk between these proteins can regulate proliferation and development by preventing or enhancing cell growth and cell death as the levels of heat shock proteins vary in response to environmental stress or disease.

scholarly journals Molecular chaperones and heat shock proteins in atherosclerosis

2012 ◽  
Vol 302 (3) ◽  
pp. H506-H514 ◽  
Author(s):  
Qingbo Xu ◽  
Bernhard Metzler ◽  
Marjan Jahangiri ◽  
Kaushik Mandal
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Molecular Chaperones ◽  
Mammalian Cells ◽  
Vessel Wall ◽  
Protective Role ◽  
Research Field ◽  
Stressed Cells ◽  
Shock Proteins ◽  
Prevention Of Atherosclerosis

In response to stress stimuli, mammalian cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs). HSPs are a family of proteins serving as molecular chaperones that prevent the formation of nonspecific protein aggregates and assist proteins in the acquisition of their native structures. Physiologically, HSPs play a protective role in the homeostasis of the vessel wall but have an impact on immunoinflammatory processes in pathological conditions involved in the development of atherosclerosis. For instance, some members of HSPs have been shown to have immunoregulatory properties and modification of innate and adaptive response to HSPs, and can protect the vessel wall from the disease. On the other hand, a high degree of sequence homology between microbial and mammalian HSPs, due to evolutionary conservation, carries a risk of misdirected autoimmunity against HSPs expressed on the stressed cells of vascular endothelium. Furthermore, HSPs and anti-HSP antibodies have been shown to elicit production of proinflammatory cytokines. Potential therapeutic use of HSP in prevention of atherosclerosis involves achieving optimal balance between protective and immunogenic effects of HSPs and in the progress of research on vaccination. In this review, we update the progress of studies on HSPs and the integrity of the vessel wall, discuss the mechanism by which HSPs exert their role in the disease development, and highlight the potential clinic translation in the research field.

Role of extracellular signal-regulated kinase (ERK) signaling in nucleotide excision repair and genotoxicity in response to As(III) and Pb(II)

2008 ◽  
Vol 80 (12) ◽  
pp. 2735-2750
Author(s):  
Ju-Pi Li ◽  
Chun-Yu Wang ◽  
Yen-An Tang ◽  
Yun-Wei Lin ◽  
Jia-Ling Yang
Keyword(s):  
Signaling Pathways ◽  
Nucleotide Excision Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Erk Signaling ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Nucleotide Excision

Arsenic and lead can induce genetic injuries and epigenetic signaling pathways in cultured mammalian cells. To test whether signaling pathways affect the extent of genetic injuries, we explored the impacts of extracellular signal-regulated kinase 1 and 2 (ERK) on nucleotide excision repair (NER), cytotoxicity, and genotoxicity following sodium arsenite [As(III)] and lead acetate [Pb(II)]. Sustained ERK activation was observed in human cells exposed to As(III) and Pb(II). As(III) inhibited the cellular NER synthesis capability; conversely, Pb(II) stimulated it. ERK activation contributed to the As(III)-induced NER inhibition and micronucleus formation. In contrast, this signal was required for inducing cellular NER activity and preventing mutagenesis following Pb(II). ERK activation by Pb(II) was dependent on protein kinase C (PKCα) that also exhibited anti-mutagenicity. Enforced expression of ERK signaling markedly elevated the cellular NER activity, which was suppressed by As(III). Nonetheless, ERK activation could counteract the cytotoxicity caused by these two metals. Together, the results indicate that pro-survival ERK signaling exhibits dual and opposing impacts on NER process following As(III) and Pb(II) exposures. The findings also suggest that ERK is an important epigenetic signaling in the determination of metal genotoxicity.

scholarly journals Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death.

1996 ◽  
Vol 133 (5) ◽  
pp. 1041-1051 ◽  
Author(s):  
M D Jacobsen ◽  
M Weil ◽  
M C Raff
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mammalian Cell ◽  
Mammalian Cells ◽  
Apoptotic Cell ◽  
Interleukin 1 ◽  
Cell Types ◽  
Cysteine Proteases ◽  
A Cell ◽  
Bona Fide

In the accompanying paper by Weil et al. (1996) we show that staurosporine (STS), in the presence of cycloheximide (CHX) to inhibit protein synthesis, induces apoptotic cell death in a large variety of nucleated mammalian cell types, suggesting that all nucleated mammalian cells constitutively express all of the proteins required to undergo programmed cell death (PCD). The reliability of that conclusion depends on the evidence that STS-induced, and (STS + CHS)-induced, cell deaths are bona fide examples of PCD. There is rapidly accumulating evidence that some members of the Ced-3/Interleukin-1 beta converting enzyme (ICE) family of cysteine proteases are part of the basic machinery of PCD. Here we show that Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a cell-permeable, irreversible, tripeptide inhibitor of some of these proteases, suppresses STS-induced and (STS + CHX)-induced cell death in a wide variety of mammalian cell types, including anucleate cytoplasts, providing strong evidence that these are all bona fide examples of PCD. We show that the Ced-3/ICE family member CPP32 becomes activated in STS-induced PCD, and that Bcl-2 inhibits this activation. Most important, we show that, in some cells at least, one or more CPP32-family members, but not ICE itself, is required for STS-induced PCD. Finally, we show that zVAD-fmk suppresses PCD in the interdigital webs in developing mouse paws and blocks the removal of web tissue during digit development, suggesting that this inhibition will be a useful tool for investigating the roles of PCD in various developmental processes.

scholarly journals Dynamic control of Hsf1 during heat shock by a chaperone switch and phosphorylation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Xu Zheng ◽  
Joanna Krakowiak ◽  
Nikit Patel ◽  
Ali Beyzavi ◽  
Jideofor Ezike ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Heat Shock ◽  
Signaling Pathways ◽  
Molecular Chaperones ◽  
Stress Resistance ◽  
Dynamic Control ◽  
Protein Homeostasis ◽  
Unfolded Proteins ◽  
Cell Signaling Pathways ◽  
Chaperone Hsp70

Heat shock factor (Hsf1) regulates the expression of molecular chaperones to maintain protein homeostasis. Despite its central role in stress resistance, disease and aging, the mechanisms that control Hsf1 activity remain unresolved. Here we show that in budding yeast, Hsf1 basally associates with the chaperone Hsp70 and this association is transiently disrupted by heat shock, providing the first evidence that a chaperone repressor directly regulates Hsf1 activity. We develop and experimentally validate a mathematical model of Hsf1 activation by heat shock in which unfolded proteins compete with Hsf1 for binding to Hsp70. Surprisingly, we find that Hsf1 phosphorylation, previously thought to be required for activation, in fact only positively tunes Hsf1 and does so without affecting Hsp70 binding. Our work reveals two uncoupled forms of regulation - an ON/OFF chaperone switch and a tunable phosphorylation gain - that allow Hsf1 to flexibly integrate signals from the proteostasis network and cell signaling pathways.

Molecular chaperones as therapeutic targets in amyotrophic lateral sclerosis

2005 ◽  
Vol 33 (4) ◽  
pp. 551-552 ◽  
Author(s):  
B. Kalmar ◽  
D. Kieran ◽  
L. Greensmith
Keyword(s):  
Cell Death ◽  
Amyotrophic Lateral Sclerosis ◽  
Heat Shock ◽  
Molecular Chaperones ◽  
Apoptotic Cell ◽  
Structural Repair ◽  
Cell Death Pathway ◽  
Shock Proteins ◽  
Intracellular Aggregates ◽  
Lateral Sclerosis

Neurodegenerative diseases are characterized by a number of common hallmarks, such as the presence of intracellular aggregates and activation of the apoptotic cell-death pathway. Intracellular chaperones, responsible for protein integrity and structural repair, may play a crucial role in the progression of a disease. In this paper, we aim to summarize our understanding of the role and potential of a particular family of chaperones, the heat-shock proteins, in neurodegeneration, by focusing our discussion on models of motoneuron death.

scholarly journals Heat Shock Protein 70 Protects from Caspase-Independent Programmed Cell Death via Suppression of Stress Kinase JNK

2001 ◽  
Vol 1 ◽  
pp. 36-36 ◽  
Author(s):  
Vladimir L. Gabai ◽  
Anatoli B. Meriin ◽  
Julia A. Yaglom ◽  
Dick D. Mosser ◽  
Michael Y. Sherman
Keyword(s):  
Cell Death ◽  
Heat Shock ◽  
Programmed Cell Death ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Stress Kinase

scholarly journals Autophagy and cell death: The jury's still out

2012 ◽  
Vol 34 (2) ◽  
pp. 14-19
Author(s):  
Jon D. Lane ◽  
Virginie M.S. Betin ◽  
Lilith Mannack ◽  
Tom D.B. MacVicar
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Mammalian Cells ◽  
Autophagic Cell Death ◽  
Circumstantial Evidence ◽  
Innocent Bystander ◽  
Catastrophic Loss ◽  
A Cell ◽  
Cell Suicide ◽  
Timely Death

Since the publication of seminal work in the early 1970s by John Kerr and Andrew Wyllie1, we have been aware that mammalian cells have the genetically encoded capability to give up the ghost and trigger a highly conserved cell-suicide pathway called apoptosis. Not content with this important knowledge, many researchers have spent the intervening years attempting to identify and characterize other ‘programmed cell death’ (PCD) mechanisms that might also have important roles in development and disease. One of these was ‘autophagy’, a process by which cells became vacuolated and progressively devoid of cytoplasm. Over the years, ‘autophagic cell death’ has been linked with the timely death of cells in development, as well as the catastrophic loss of cells in several important human diseases. But is autophagy truly a cell death mechanism in its own right? Perhaps it is just an innocent bystander, unfairly accused on the basis of flimsy circumstantial evidence? The jury may finally be poised to return a decisive verdict….

scholarly journals Cellular Stress Responses: Cell Survival and Cell Death

2010 ◽  
Vol 2010 ◽  
pp. 1-23 ◽  
Author(s):  
Simone Fulda ◽  
Adrienne M. Gorman ◽  
Osamu Hori ◽  
Afshin Samali
Keyword(s):  
Cell Death ◽  
Stress Responses ◽  
Cellular Stress ◽  
World Health ◽  
Health Issues ◽  
Survival Pathways ◽  
Cellular Stress Responses ◽  
A Cell ◽  
Exogenous Factors ◽  
Stressed Cell

Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective or destructive stress response depends to a large extent on the nature and duration of the stress as well as the cell type. Also, there is often the interplay between these responses that ultimately determines the fate of the stressed cell. The mechanism by which a cell dies (i.e., apoptosis, necrosis, pyroptosis, or autophagic cell death) depends on various exogenous factors as well as the cell's ability to handle the stress to which it is exposed. The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer.

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