• Molecules and Cells
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• 제41권9호
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• pp.818-829
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• 2018

Significant research efforts are ongoing to elucidate the complex molecular mechanisms underlying amyotrophic lateral sclerosis (ALS), which may in turn pinpoint potential therapeutic targets for treatment. The ALS research field has evolved with recent discoveries of numerous genetic mutations in ALS patients, many of which are in genes encoding RNA binding proteins (RBPs), including TDP-43, FUS, ATXN2, TAF15, EWSR1, hnRNPA1, hnRNPA2/B1, MATR3 and TIA1. Accumulating evidence from studies on these ALS-linked RBPs suggests that dysregulation of RNA metabolism, cytoplasmic mislocalization of RBPs, dysfunction in stress granule dynamics of RBPs and increased propensity of mutant RBPs to aggregate may lead to ALS pathogenesis. Here, we review current knowledge of the biological function of these RBPs and the contributions of ALS-linked mutations to disease pathogenesis.

• Animal cells and systems
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• 제9권4호
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• pp.181-190
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• 2005

BIRPs (BIR containing Proteins) which contain one to three BIR domains constitute a highly conserved family from yeast to human. BIR domains mediate the interaction of BIRPs with various other proteins. Some of the members acquire a Ring domain which acts as an E3 ubiquitin ligase. The first member of BIRPs identified in the baculovirus was found as an inhibitor of apoptosis and most of the family members in the other species have been recognized to have the same function which bind to and inhibit caspases, thereby suppresses apoptotic cell death. But an increasing number of evidences indicate that BIRPs are involved in various cellular events such as cell division, control of cell cycle, signal transduction, cell migration, innate immunity as well as regulation of apoptosis. In this review, we summarize the structural and functional features of the BIRPs, especially focus on the various functions of BIRPs unrelated to regulation of apoptosis by the recent findings.

• Molecules and Cells
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• 제42권4호
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• pp.285-291
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• 2019

Eukaryotic cells use conserved quality control mechanisms to repair or degrade defective proteins, which are synthesized at a high rate during proteotoxic stress. Quality control mechanisms include molecular chaperones, the ubiquitin-proteasome system, and autophagic machinery. Recent research reveals that during autophagy, membrane-bound organelles are selectively sequestered and degraded. Selective autophagy is also critical for the clearance of excess or damaged protein complexes (e.g., proteasomes and ribosomes) and membrane-less compartments (e.g., protein aggregates and ribonucleoprotein granules). As sessile organisms, plants rely on quality control mechanisms for their adaptation to fluctuating environments. In this mini-review, we highlight recent work elucidating the roles of selective autophagy in the quality control of proteins and RNA in plant cells. Emphasis will be placed on selective degradation of membrane-less compartments and protein complexes in the cytoplasm. We also propose possible mechanisms by which defective proteins are selectively recognized by autophagic machinery.

• Molecules and Cells
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• 제45권6호
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• pp.353-361
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• 2022

Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial-mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.

• 대한화학회지
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• 제67권5호
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• pp.348-352
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• 2023

p97, a universally conserved AAA+ ATPase, holds a central position in the ubiquitin-proteasome system, orchestrating myriad cellular activities with significant therapeutic implications. This protein primarily interacts with a diverse set of adaptor proteins through its N-terminal domain (NTD), which is structurally located at the periphery of the D1 hexamer ring. While there have been numerous structural elucidations of p97 complexed with adaptor proteins, the stoichiometry has remained elusive. In this work, we present the crystal structure of the p97-N/D1 hexamer bound to the FAF1-UBX domain at a resolution of 3.1 Å. Our findings reveal a 6:6 stoichiometry between the p97 hexamer and FAF1-UBX domain, deepening our understanding from preceding structural studies related to p97-NTD and UBX domain-containing proteins. These insights lay the groundwork for potential therapeutic interventions addressing cancer and neurodegenerative diseases.

• International Journal of Oral Biology
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• 제49권2호
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• pp.42-47
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• 2024

Ophiopogonin D (OPD) is a steroidal glycoside derived from Ophiopogon japonicus, a traditional Chinese medicine with diverse biological activities, including antithrombosis, anti-inflammation, and antitussive effects. To investigate the cellular effects and mechanisms of OPD on oral squamous cell carcinoma, cell viability was explored, and the effects of OPD on cell cycle regulators, apoptotic marker proteins, and key proteins involved in metastasis and signaling pathways were examined by MTT assay and Western blotting in YD38 cells. OPD strongly inhibited cell proliferation and induced caspase-dependent apoptosis of YD38 cells by suppressing the cell cycle and activating caspase-3 and poly ADP ribose polymerase. Additionally, OPD suppressed the expression of vital proteins regulating metastasis and proliferation within the integrin/matrix metalloproteinases/FAK and AKT/PI3K/mTor pathways. Thus, OPD can be a potential treatment candidate for gingival cancer.

• BMB Reports
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• 제35권4호
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• pp.353-357
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• 2002

Singlet oxygen ($^1O_2$) is highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. The oxyR gene product regulates the expression of the enzymes and proteins that are needed for cellular protection against oxidative stress. In this study, the role of oxyR in cellular defense against a singlet oxygen was investigated using Escherichia coli oxyR mutant strains. Upon exposure to methylene blue and visible light, which generates singlet oxygen, the oxyR overexpression mutant was much more resistant to singlet oxygen-mediated cellular damage when compared to the oxyR deletion mutant in regard to growth kinetics, viability and protein oxidation. Induction and inactivation of major antioxidant enzymes, such as superoxide desmutase and catalase, were observed after their exposure to a singlet oxygen generating system in both oxyR strains. However, the oxyR overexpression mutant maintained significantly higher activities of anticxidant enzymes than did the oxyR deletion mutant. These results suggest that the oxyR regulon plays an important protective role in singlet oxygen-mediated cellular damage, presumably through the protection of antioxidant enzymes.

• BMB Reports
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• 제49권8호
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• pp.449-454
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• 2016

Stress Granules (SGs) are microscopically visible, phase dense aggregates of translationally stalled messenger ribonucleoprotein (mRNP) complexes formed in response to distinct stress conditions. It is generally considered that SG formation is induced to protect cells from conditions of stress. The precise constituents of SGs and the mechanism through which SGs are dynamically regulated in response to stress are not completely understood. Hence, it is important to identify proteins which regulate SG assembly and disassembly. In the present study, we report Neuregulin-2 (NRG2) as a novel component of SGs; furthermore, depletion of NRG2 potently inhibits SG formation. We also demonstrate that NRG2 specifically localizes to SGs under various stress conditions. Knockdown of NRG2 has no effect on stress-induced polysome disassembly, suggesting that the component does not influence early step of SG formation. It was also observed that reduced expression of NRG2 led to marginal increase in cell survival under arsenite-induced stress.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2001년도 한국생물과학협회 학술발표대회
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• pp.193.1-193
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• 2001

No Abstract, See Full Text

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5317-5323
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• 2013

Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of $r^2$=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an $IC_{50}$ value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.