scholarly journals Cell adaptation to aneuploidy by the environmental stress response dampens induction of the cytosolic unfolded protein response

2021 ◽  
pp. mbc.E21-03-0104
Author(s):  
Andrew J. Kane ◽  
Christopher M. Brennan ◽  
Acer E. Xu ◽  
Eric J. Solís ◽  
Allegra Terhorst ◽  
...  
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Environmental Stress ◽  
Unfolded Protein Response ◽  
Yeast Cells ◽  
Heat Shock Factor 1 ◽  
Environmental Stress Response ◽  
Single Chromosome ◽  
Unfolded Protein ◽  
Protein Response

Aneuploid yeast cells are in a chronic state of proteotoxicity yet do not constitutively induce the cytosolic unfolded protein response (HSR) by Heat shock factor 1 (Hsf1). Here, we demonstrate that an active environmental stress response (ESR), a hallmark of aneuploidy across different models, suppresses Hsf1 induction in models of single chromosome gain. Furthermore, engineered activation of the ESR in the absence of stress was sufficient to suppress Hsf1 activation in euploid cells by subsequent heat shock while increasing thermotolerance and blocking formation of heat-induced protein aggregates. Suppression of the ESR in aneuploid cells resulted in longer cell doubling times and decreased viability in the presence of additional proteotoxicity. Lastly, we show that in euploids Hsf1 induction by heat shock is curbed by the ESR. Strikingly, we found a similar relationship between the ESR and the HSR using an inducible model of aneuploidy. Our work explains a long-standing paradox in the field and provides new insights into conserved mechanisms of proteostasis with potential relevance to cancers associated with aneuploidy.

scholarly journals C. elegans electrotaxis behavior is modulated by heat shock response and unfolded protein response signaling pathways

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shane K. B. Taylor ◽  
Muhammad H. Minhas ◽  
Justin Tong ◽  
P. Ravi Selvaganapathy ◽  
Ram K. Mishra ◽  
...  
Keyword(s):  
Stress Response ◽  
Environmental Stress ◽  
Unfolded Protein Response ◽  
Multiple Stress ◽  
C Elegans ◽  
Unfolded Protein ◽  
Transient Activation ◽  
Directional Motion ◽  
The Face ◽  
Protein Response

AbstractThe nematode C. elegans is a leading model to investigate the mechanisms of stress-induced behavioral changes coupled with biochemical mechanisms. Our group has previously characterized C. elegans behavior using a microfluidic-based electrotaxis device, and showed that worms display directional motion in the presence of a mild electric field. In this study, we describe the effects of various forms of genetic and environmental stress on the electrotactic movement of animals. Using exposure to chemicals, such as paraquat and tunicamycin, as well as mitochondrial and endoplasmic reticulum (ER) unfolded protein response (UPR) mutants, we demonstrate that chronic stress causes abnormal movement. Additionally, we report that pqe-1 (human RNA exonuclease 1 homolog) is necessary for the maintenance of multiple stress response signaling and electrotaxis behavior of animals. Further, exposure of C. elegans to several environmental stress-inducing conditions revealed that while chronic heat and dietary restriction caused electrotaxis speed deficits due to prolonged stress, daily exercise had a beneficial effect on the animals, likely due to improved muscle health and transient activation of UPR. Overall, these data demonstrate that the electrotaxis behavior of worms is susceptible to cytosolic, mitochondrial, and ER stress, and that multiple stress response pathways contribute to its preservation in the face of stressful stimuli.

scholarly journals The environmental stress response causes ribosome loss in aneuploid yeast cells

2020 ◽  
Vol 117 (29) ◽  
pp. 17031-17040 ◽  
Author(s):  
Allegra Terhorst ◽  
Arzu Sandikci ◽  
Abigail Keller ◽  
Charles A. Whittaker ◽  
Maitreya J. Dunham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stress Response ◽  
Stationary Phase ◽  
Environmental Stress ◽  
Budding Yeast ◽  
Expression Patterns ◽  
Yeast Cells ◽  
Specific Gene ◽  
Environmental Stress Response ◽  
Cellular Stresses

Aneuploidy, a condition characterized by whole chromosome gains and losses, is often associated with significant cellular stress and decreased fitness. However, how cells respond to the aneuploid state has remained controversial. In aneuploid budding yeast, two opposing gene-expression patterns have been reported: the “environmental stress response” (ESR) and the “common aneuploidy gene-expression” (CAGE) signature, in which many ESR genes are oppositely regulated. Here, we investigate this controversy. We show that the CAGE signature is not an aneuploidy-specific gene-expression signature but the result of normalizing the gene-expression profile of actively proliferating aneuploid cells to that of euploid cells grown into stationary phase. Because growth into stationary phase is among the strongest inducers of the ESR, the ESR in aneuploid cells was masked when stationary phase euploid cells were used for normalization in transcriptomic studies. When exponentially growing euploid cells are used in gene-expression comparisons with aneuploid cells, the CAGE signature is no longer evident in aneuploid cells. Instead, aneuploid cells exhibit the ESR. We further show that the ESR causes selective ribosome loss in aneuploid cells, providing an explanation for the decreased cellular density of aneuploid cells. We conclude that aneuploid budding yeast cells mount the ESR, rather than the CAGE signature, in response to aneuploidy-induced cellular stresses, resulting in selective ribosome loss. We propose that the ESR serves two purposes in aneuploid cells: protecting cells from aneuploidy-induced cellular stresses and preventing excessive cellular enlargement during slowed cell cycles by down-regulating translation capacity.

scholarly journals HY5, a positive regulator of light signaling, negatively controls the unfolded protein response inArabidopsis

2017 ◽  
Vol 114 (8) ◽  
pp. 2084-2089 ◽  
Author(s):  
Ganesh M. Nawkar ◽  
Chang Ho Kang ◽  
Punyakishore Maibam ◽  
Joung Hun Park ◽  
Young Jun Jung ◽  
...  
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Molecular Mechanism ◽  
26S Proteasome ◽  
Light Signaling ◽  
Unfolded Protein ◽  
Er Stress Response ◽  
The Unfolded Protein Response ◽  
Protein Response

Light influences essentially all aspects of plant growth and development. Integration of light signaling with different stress response results in improvement of plant survival rates in ever changing environmental conditions. Diverse environmental stresses affect the protein-folding capacity of the endoplasmic reticulum (ER), thus evoking ER stress in plants. Consequently, the unfolded protein response (UPR), in which a set of molecular chaperones is expressed, is initiated in the ER to alleviate this stress. Although its underlying molecular mechanism remains unknown, light is believed to be required for the ER stress response. In this study, we demonstrate that increasing light intensity elevates the ER stress sensitivity of plants. Moreover, mutation of the ELONGATED HYPOCOTYL 5 (HY5), a key component of light signaling, leads to tolerance to ER stress. This enhanced tolerance ofhy5plants can be attributed to higher expression of UPR genes. HY5 negatively regulates the UPR by competing with basic leucine zipper 28 (bZIP28) to bind to the G-box–like element present in the ER stress response element (ERSE). Furthermore, we found that HY5 undergoes 26S proteasome-mediated degradation under ER stress conditions. Conclusively, we propose a molecular mechanism of crosstalk between the UPR and light signaling, mediated by HY5, which positively mediates light signaling, but negatively regulates UPR gene expression.

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