• BMB Reports
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• v.48 no.9
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• pp.487-488
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• 2015

The ubiquitin-proteasome system and the autophagy lysosome system are the two major protein degradation machineries in eukaryotic cells. These two systems coordinate the removal of unwanted intracellular materials, but the mechanism by which they achieve this synchronization is largely unknown. The ubiquitination of substrates serves as a universal degradation signal for both systems. Our study revealed that the amino-terminal Arg, a canonical N-degron in the ubiquitin-proteasome system, also acts as a degradation signal in autophagy. We showed that many ER residents, such as BiP, contain evolutionally conserved arginylation permissive pro-N-degrons, and that certain inducers like dsDNA or proteasome inhibitors cause their translocation into the cytoplasm where they bind misfolded proteins and undergo amino-terminal arginylation by arginyl transferase 1 (ATE1). The amino-terminal Arg of BiP binds p62, which triggers p62 oligomerization and enhances p62-LC3 interaction, thereby stimulating autophagic delivery and degradation of misfolded proteins, promoting cell survival. This study reveals a novel ubiquitin-independent mechanism for the selective autophagy pathway, and provides an insight into how these two major protein degradation pathways communicate in cells to dispose the unwanted proteins. [BMB Reports 2015; 48(9): 487-488]

• BMB Reports
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• v.49 no.7
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• pp.388-393
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• 2016

Although brown adipose tissue is important with regard to energy balance, the molecular mechanism of brown adipocyte differentiation has not been extensively studied. Specifically, regulation factors at the level of protein modification are largely unknown. In this study, we examine the changes in the expression level of enzymes which are involved in protein lysine methylation during brown adipocyte differentiation. Several enzymes, in this case SUV420H2, PRDM9, MLL3 and JHDM1D, were found to be up-regulated. On the other hand, Set7/9 was significantly down-regulated. In the case of SUV420H2, the expression level increased sharply during brown adipocyte differentiation, whereas the expression of SUV420H2 was marginally enhanced during the white adipocyte differentiation. The knock-down of SUV420H2 caused the suppression of brown adipocyte differentiation, as compared to a scrambled control. These results suggest that SUV420H2, a methyltransferase, is involved in brown adipocyte differentiation, and that the methylation of protein lysine is important in brown adipocyte differentiation.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.101-108
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• 2018

G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs. Despite the clinical importance of GPCRs, studies on the genotype-phenotype relationship of GPCR natural variants have been limited to a few GPCRs such as b-adrenergic receptors and opioid receptors. Comprehensive understanding of non-synonymous natural variations within GPCRs would help to predict the unknown genotype-phenotype relationship and yet-to-be-discovered natural variants. Here, we analyzed the non-synonymous natural variants of all non-olfactory GPCRs available from a public database, UniProt. The results suggest that non-synonymous natural variations occur extensively within the GPCR superfamily especially in the N-terminus and transmembrane domains. Within the transmembrane domains, natural variations observed more frequently in the conserved residues, which leads to disruption of the receptor function. Our analysis also suggests that only few non-synonymous natural variations have been studied in efforts to link the variations with functional consequences.

• Molecules and Cells
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• v.40 no.5
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• pp.315-321
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• 2017

The inositol polyphosphates are a group of multifunctional signaling metabolites whose synthesis is catalyzed by a family of inositol kinases that are evolutionarily conserved from yeast to humans. Inositol polyphosphate multikinase (IPMK) was first identified as a subunit of the arginine-responsive transcription complex in budding yeast. In addition to its role in the production of inositol tetrakis- and pentakisphosphates ($IP_4$ and $IP_5$), IPMK also exhibits phosphatidylinositol 3-kinase (PI3-kinase) activity. Through its PI3-kinase activity, IPMK activates Akt/PKB and its downstream signaling pathways. IPMK also regulates several protein targets non-catalytically via protein-protein interactions. These non-catalytic targets include cytosolic signaling factors and transcription factors in the nucleus. In this review, we highlight the many known functions of mammalian IPMK in controlling cellular signaling networks and discuss future challenges related to clarifying the unknown roles IPMK plays in physiology and disease.

• The Plant Pathology Journal
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• v.35 no.5
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• pp.530-537
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• 2019

Fuji, a major apple cultivar in Korea, is susceptible to white rot. Apple white rot disease appears on the stem and fruit; the development of which deteriorates fruit quality, resulting in decreases in farmers' income. Thus, it is necessary to characterize molecular markers related to apple white rot resistance. In this study, we screened for differentially expressed genes between uninfected apple fruits and those infected with Botryosphaeria dothidea, the fungal pathogen that causes white rot. Antimicrobial tests suggest that a gene expression involved in the synthesis of the substance inhibiting the growth of B. dothidea in apples was induced by pathogen infection. We identified seven transcripts induced by the infection. The seven transcripts were homologous to genes encoding a flavonoid glucosyltransferase, a metallothionein-like protein, a senescence-induced protein, a chitinase, a wound-induced protein, and proteins of unknown function. These genes have functions related to responses to environmental stresses, including pathogen infections. Our results can be useful for the development of molecular markers for early detection of the disease or for use in breeding white rotresistant cultivars.

• CELLMED
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• v.13 no.6
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• pp.7.1-7.6
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• 2023

Raphanus sativus L. has been reported to have anti-inflammatory and anti-tumor activity. However, the anti-inflammatory effect and mechanism of action of the Raphanus sativus L. seeds (RSS) with or without oil are still unknown. This study was undertaken to investigate the in-vitro anti-inflammatory effect with or without oil in the RSS on RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Results showed the suppressed LPS-induced secretion of pro-inflammatory mediators such as nitric oxide (NO), inflammatory cytokine (IL-6, TNF-α). Additionally, a decrease in protein expression of iNOS was observed, but nuclear translocation of NF-κB p65 was not inhibited. To elucidate the underlying mechanism of the anti-inflammatory effect of RSS, the involvement of mitogen-activated protein kinase (MAPK) signaling pathways was examined. We also found that RSS blocked LPS-induced phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK) signaling but did not affect the phosphorylation of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2. These results suggest that RSS may have potential as an anti-inflammatory agent through the inhibition of LPS-induced inflammatory cytokine production via regulation of the JNK pathway.

• Development and Reproduction
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• v.27 no.3
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• pp.159-165
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• 2023

The Ruvb-like AAA ATPase1 (Ruvbl1; also known as Pontin) is an evolutionary conserved protein belonging to the adenosine triphosphates associated with diverse cellular activities (AAA+) superfamily of ATPases. Ruvbl1 is a component of various protein supercomplexes and is involved in a variety of cellular activities, including chromatin remodeling, DNA damage repair, and mitotic spindle assembly however, the developmental significance of this protein is unknown and needs detailed investigation. We investigated the developmental significance of Ruvbl1 in multiciliated cells of the Xenopus laevis epidermis since ruvbl1 is expressed in the multiciliated cells and pronephros during X. laevis embryogenesis. The knockdown of ruvbl1 significantly impaired cilia-driven fluid flow and basal body polarity in the X. laevis epidermis compared to control embryos, but did not affect cilia morphology. Our results suggest that Ruvbl1 plays a significant role in embryonic development by regulating ciliary beating; however, further investigation is needed to determine the mechanisms involved.

• Journal of Nutrition and Health
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• v.4 no.1
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• pp.63-67
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• 1971

The nitrogen content and free amino acids were determined from the saute of mong bean paste which is one of the important protein sources on Korean diet. During the saute' process of mong-bean paste, valine, r-aminobutyrate, glutamine, arginine, methionine, and unknown acids were lost, but, proline, lysine, homoserine, and tyrosine were detected.

• Korean Journal of Oriental Medicine
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• v.6 no.1
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• pp.99-105
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• 2000

Lithium, a simple monovalent cation, is the mainstay in the treatment of manic-depressive illness, but despite extensive research, its mechanism of action remains to be elucidated. Because lithium requires chronic administration for therapeutic efficacy and because its beneficial effects last well beyond its discontinuation, it has been postulated that lithium may exert major effects at the genomic level. We have previously shown that Yungmijihwangwon (YM) increase TH protein expression through antioxidant activity and unknown effects in vivo. In the pressent study, we have sought to determine if lithium in herbal medicine also increases the expression of endogenous gene known to be regulated by AP-1 and have therefore investigated the effects of herbal medicine on tyrosine hydroxylase (TH) levels. Male mice were treated with LiCl and herbal medicine for 30 days, and TH levels and dopamine level were measured in striatum using immunoblotting and ECD-HPLC. Herbal medicine treatment resulted in statistically nonsignificant increase in TH levels in mouse striatum. The precise therapeutic relevance of these effects is presently unknown.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.53-56
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• 2016

Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012. We report another case of FMF in Korea in which the patient presented with a month-long fever without serositis. After treatment with colchicine was initiated, the patient's symptoms quickly subsided. The response to colchicine was helpful for diagnosis. We compare the FMF genotypes in Korea with in other countries. Studying FMF cases in Korea will help establish the best MEFV exons to use for screening and diagnosis of Korean FMF.