Bax induces activation of the unfolded protein response by inducing <i>HAC1</i> mRNA splicing in <i>Saccharomyces cerevisiae</i>

Çakır, Birsen

doi:10.1002/yea.2918

Cited by 10 publications

(8 citation statements)

References 66 publications

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“…The method of qRT-PCR was previously described (Yamauchi and Izawa, 2016). The oligonucleotide sequences of the primers used for qRT-PCR were as follows: KAR2 , 5′-AGACTAAGCGCTGGCAAGCT-3′ and 5′-ACCACGAAAAGGGCGTACAG-3′; ACT1 , 5′-TTGGATTCCGGTGATGGTGTTACT-3′ and 5′-TGAAGAAGATTGAGCAGCGGTTTG-3′ (Takahashi et al, 2011; Cakir, 2012). The splicing of HAC1 mRNA was monitored by the methods of Promlek et al (2011).…”

Section: Methodsmentioning

confidence: 99%

Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein Response in Saccharomyces cerevisiae

Kawazoe

Izawa

2017

Front. Microbiol.

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Since acetic acid inhibits the growth and fermentation ability of Saccharomyces cerevisiae, it is one of the practical hindrances to the efficient production of bioethanol from a lignocellulosic biomass. Although extensive information is available on yeast response to acetic acid stress, the involvement of endoplasmic reticulum (ER) and unfolded protein response (UPR) has not been addressed. We herein demonstrated that acetic acid causes ER stress and induces the UPR. The accumulation of misfolded proteins in the ER and activation of Ire1p and Hac1p, an ER-stress sensor and ER stress-responsive transcription factor, respectively, were induced by a treatment with acetic acid stress (>0.2% v/v). Other monocarboxylic acids such as propionic acid and sorbic acid, but not lactic acid, also induced the UPR. Additionally, ire1Δ and hac1Δ cells were more sensitive to acetic acid than wild-type cells, indicating that activation of the Ire1p-Hac1p pathway is required for maximum tolerance to acetic acid. Furthermore, the combination of mild acetic acid stress (0.1% acetic acid) and mild ethanol stress (5% ethanol) induced the UPR, whereas neither mild ethanol stress nor mild acetic acid stress individually activated Ire1p, suggesting that ER stress is easily induced in yeast cells during the fermentation process of lignocellulosic hydrolysates. It was possible to avoid the induction of ER stress caused by acetic acid and the combined stress by adjusting extracellular pH.

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Section: Methodsmentioning

confidence: 99%

Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein Response in Saccharomyces cerevisiae

Kawazoe

Izawa

2017

Front. Microbiol.

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“…By analogy with ricin, we can speculate that PAP may interfere with UPR therefore causing ER stress induced cell death. We recently showed that Bax expression induced the UPR in yeast and this was associated with HAC1 mRNA splicing 74. Yeast cells deficient for yeast bax inhibitor (∆ bxi1 ) are not only more sensitive to ER stress-inducing drugs but also have a decreased UPR 75.…”

Section: Discussionmentioning

confidence: 99%

Arabidopsis Bax Inhibitor-1 inhibits cell death induced by pokeweed antiviral protein in Saccharomyces cerevisae

Çakır

Tumer

2015

MIC

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Apoptosis is an active form of programmed cell death (PCD) that plays critical roles in the development, differentiation and resistance to pathogens in multicellular organisms. Ribosome inactivating proteins (RIPs) are able to induce apoptotic cell death in mammalian cells. In this study, using yeast as a model system, we showed that yeast cells expressing pokeweed antiviral protein (PAP), a single-chain ribosome-inactivating protein, exhibit apoptotic-like features, such as nuclear fragmentation and ROS production. We studied the interaction between PAP and AtBI-1 (Arabidopsis thaliana Bax Inhibitor-1), a plant anti-apoptotic protein, which inhibits Bax induced cell death. Cells expressing PAP and AtBI-1 were able to survive on galactose media compared to PAP alone, indicating a reduction in the cytotoxicity of PAP in yeast. However, PAP was able to depurinate the ribosomes and to inhibit total translation in the presence of AtBI-1. A C-terminally deleted AtBI-1 was able to reduce the cytotoxicity of PAP. Since anti-apoptotic proteins form heterodimers to inhibit the biological activity of their partners, we used a co-immunoprecipitation assay to examine the binding of AtBI-1 to PAP. Both full length and C-terminal deleted AtBI-1 were capable of binding to PAP. These findings indicate that PAP induces cell death in yeast and AtBI-1 inhibits cell death induced by PAP without affecting ribosome depurination and translation inhibition.

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“…In S. cerevisiae expression systems, the production and accumulation of misfolded proteins, especially the overexpression of proteins from multiple copies of a gene, are key to the efficient expression of heterologous proteins [33] . These proteins cannot be properly folded, so they will be accumulated in the ER, triggering the ER-associated protein degradation (ERAD) pathway, resulting in degradation by ER protease.…”

Section: Overexpression Of Hac1 Enhances the Expression Of Heterologomentioning

confidence: 99%

Expression and function of an HAC1-regulated multi-copy xylanase gene in Saccharomyces cerevisiae

Zhang

Bao

et al. 2020

Preprint

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To investigate the effects of transcription factor HAC1, which is involved in the unfolded protein response pathway, on the expression of xynB in Saccharomyces cerevisiae , we used overlap extension polymerase chain reaction (PCR), rDNA integration, and droplet digital PCR technology to generate a S . cerevisiae strain (S8) containing eight copies of the xylanase gene, allowing high-yield secretory expression of xylanase. HAC1 was then overexpressed in the S8 strain, and the GeXP system was used to study the effects of HAC1 overexpression on the expression of genes associated with protein folding in the endoplasmic reticulum (ER). Results confirmed the constitutive secretory expression of the multiple copies of the xylanase gene in S . cerevisiae following rDNA-based integration of the expression cassette. Specifically, recombinant S . cerevisiae strain S8, containing eight copies of the xylanase gene, showed maximum xylanase expression, with a yield of 325 U/mL. However, overexpression of HAC1 further improved xylanase production by strain S8, resulting in a yield of 381 U/mL. These results confirmed that overexpression of HAC1 improves the expression of genes associated with protein folding in the ER, enhancing the protein folding and assembly functions of the ER and increasing xylanase expression.

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Bax induces activation of the unfolded protein response by inducing HAC1 mRNA splicing in Saccharomyces cerevisiae

Cited by 10 publications

References 66 publications

Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein Response in Saccharomyces cerevisiae

Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein Response in Saccharomyces cerevisiae

Arabidopsis Bax Inhibitor-1 inhibits cell death induced by pokeweed antiviral protein in Saccharomyces cerevisae

Expression and function of an HAC1-regulated multi-copy xylanase gene in Saccharomyces cerevisiae

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Bax induces activation of the unfolded protein response by inducing HAC1 mRNA splicing in Saccharomyces cerevisiae

Cited by 10 publications

References 66 publications

Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein Response in Saccharomyces cerevisiae

Acetic Acid Causes Endoplasmic Reticulum Stress and Induces the Unfolded Protein Response in Saccharomyces cerevisiae

Arabidopsis Bax Inhibitor-1 inhibits cell death induced by pokeweed antiviral protein in Saccharomyces cerevisae

Expression and function of&nbsp;an HAC1-regulated multi-copy xylanase&nbsp;gene in Saccharomyces cerevisiae

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Expression and function of an HAC1-regulated multi-copy xylanase gene in Saccharomyces cerevisiae