• Title/Summary/Keyword: unfolded protein response

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Mitochondria-mediated defense mechanisms against pathogens in Caenorhabditis elegans

  • Kwon, Sujeong;Kim, Eun Ji E.;Lee, Seung-Jae V.
    • BMB Reports
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    • v.51 no.6
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    • pp.274-279
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    • 2018

  • Mitochondria are crucial organelles that generate cellular energy and metabolites. Recent studies indicate that mitochondria also regulate immunity. In this review, we discuss key roles of mitochondria in immunity against pathogen infection and underlying mechanisms, focusing on discoveries using Caenorhabditis elegans. Various mitochondrial processes, including mitochondrial surveillance mechanisms, mitochondrial unfolded protein response ($UPR^{mt}$), mitophagy, and reactive oxygen species (ROS) production, contribute to immune responses and resistance of C. elegans against pathogens. Biological processes of C. elegans are usually conserved across phyla. Thus, understanding the mechanisms of mitochondria-mediated defense responses in C. elegans may provide insights into similar mechanisms in complex organisms, including mammals.

  • https://doi.org/10.5483/BMBRep.2018.51.6.111 인용 PDF KSCI

Direct Evaluation of the Effect of Gene Dosage on Secretion of Protein from Yeast Pichia pastoris by Expressing EGFP

  • Liu, Hailong;Qin, Yufeng;Huang, Yuankai;Chen, Yaosheng;Cong, Peiqing;He, Zuyong
    • Journal of Microbiology and Biotechnology
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    • v.24 no.2
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    • pp.144-151
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    • 2014

  • Increasing the gene copy number has been commonly used to enhance the protein expression level in the yeast Pichia pastoris. However, this method has been shown to be effective up to a certain gene copy number, and a further increase of gene dosage can result in a decrease of expression level. Evidences indicate the gene dosage effect is product-dependent, which needs to be determined when expressing a new protein. Here, we describe a direct detection of the gene dosage effect on protein secretion through expressing the enhanced green fluorescent protein (EGFP) gene under the direction of the ${\alpha}$-factor preprosequence in a panel of yeast clones carrying increasing copies of the EGFP gene (from one to six copies). Directly examined under fluorescence microscopy, we found relatively lower levels of EGFP were secreted into the culture medium at one copy and two copies, substantial improvement of secretion appeared at three copies, plateau happened at four and five copies, and an apparent decrease of secretion happened at six copies. The secretion of EGFP being limiting at four and five copies was due to abundant intracellular accumulation of proteins, observed from the fluorescence image of yeast and confirmed by western blotting, which significantly activated the unfolded protein response indicated by the up-regulation of the BiP (the KAR2 gene product) and the protein disulfide isomerase. This study implies that tagging a reporter like GFP to a specific protein would facilitate a direct and rapid determination of the optimal gene copy number for high-yield expression.

  • https://doi.org/10.4014/jmb.1308.08010 인용 PDF KSCI KPUBS HTML

Pancastatin A and B Have Selective Cytotoxicity on Glucose-Deprived PANC-1 Human Pancreatic Cancer Cells

  • Park, Hae-Ryong
    • Journal of Microbiology and Biotechnology
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    • v.30 no.5
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    • pp.733-738
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    • 2020

  • Glucose deprivation and hypoxia frequently occur in solid tumor cells, including pancreatic cancer cells. Glucose deprivation activates the unfolded protein response (UPR) and causes the up-regulation of glucose-regulated protein 78 (GRP78). Induction of GRP78 has been shown to protect cancer cells. Therefore, shutting down of GRP78 expression may be a novel strategy in anticancer drug development. Based on this understanding, a screening system established for anticancer agents that exhibit selective cytotoxicity on pancreatic cancer cells under glucose-deprived conditions. To test this hypothesis, the new compounds isolated, pancastatin A (PST-A) and B (PST-B), from Ponciri Fructus. PST-A and B were identified as glabretal triterpenoid moieties by electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopic methods. PST-A and B suppressed the accumulation of the UPR hallmark gene, GRP78, during glucose deprivation. Furthermore, PST-A and B showed selective cytotoxicity on PANC-1 pancreatic cancer cells under glucose deprivation. Interestingly, PST-A and B had no effect on these cells under normal growth conditions. Our results suggest that PST-A and B act as novel therapeutic agents to induce selective cell death in glucose-deprived pancreatic cancer cells.

  • https://doi.org/10.4014/jmb.2002.02002 인용 PDF KSCI