• BMB Reports
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• v.51 no.3
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• pp.119-125
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• 2018

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.

• BMB Reports
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• v.53 no.1
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• pp.56-63
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• 2020

The ubiquitin-proteasome system (UPS) and autophagy are two major degradative pathways of proteins in eukaryotic cells. As about 30% of newly synthesized proteins are known to be misfolded under normal cell conditions, the precise and timely operation of the UPS and autophagy to remove them as well as their tightly controlled regulation, is so important for proper cell function and survival. In the UPS, target proteins are labeled by small proteins called ubiquitin, which are then transported to the proteasome complex for degradation. Alternatively, many greatly damaged proteins are believed to be delivered to the lysosome for autophagic degradation. Although these autophagy and UPS pathways have not been considered to be directly related, many recent studies proposed their close link and dynamic interconversion. In this review, we'll focus on the several regulatory molecules that function in both UPS and autophagy and their crosstalk. Among the proposed multiple modulators, we will take a closer look at the so-called main connector of UPS-autophagy regulation, p62. Last, the functional role of p62 in the mitophagy and its implication for the pathogenesis of Parkinson's disease, one of the major neurodegenerative diseases, will be briefly reviewed.

• Journal of Integrative Natural Science
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• v.10 no.3
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• pp.141-147
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• 2017

Vascular endothelial growth factor (VEGF) is an important signaling protein involved in angiogenesis, which is the formation of new blood vessels from pre-existing vessels. Consequently, blocking of the vascular endothelial growth factor receptor (VEGFR-2) by small molecule inhibitors leads to the inhibition of cancer induced angiogenesis. In this study, we performed a two dimensional quantitative structure activity relationship (2D-QSAR) study of 38 N-Phenyl-N'-{4-(4-quinolyloxy) phenyl} urea derivatives as VEGFR-2 inhibitors based on hologram quantitative structure-activity (HQSAR). The model developed showed reasonable $q^2=0.521$ and $r^2=0.932$ values indicating good predictive ability and reliability. The atomic contribution map analysis of most active compound (compound 7) indicates that hydrogen and oxygen atoms in the side chain of ring A and oxygen atom in side chain of ring C contributes positively to the activity of the compounds. The HQSAR model developed and the atomic contribution map can serve as a guideline in designing new compounds for VEGFR-2 inhibition.

• YAKHAK HOEJI
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• v.42 no.4
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• pp.467-471
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• 1998

Numerous efforts have been made to isolate immunologically active component from Mori Cortex Radicis, since it has been used in the treatment of bronchial asthma, and immune dis order in human. Recently, we reported the purification of an anti-allergic component of the Mori Cortex Radicis. Among the fractions we prepared in the previous study, a fraction was active in the proliferation of murine lymphocytes. The active component (HHM 3-1) was elucidated as a polysaccharade with a small amount of lignin. When it was subjected to MALDI-MS by using 3-hydroxypicolinic acid as a matrix, the molecular weight of the component was estimated as 792688.2dalton. Total hexose and protein content of the component were estimated as 62.6% and 0.51%, respectively and it was composed mainly of glucose, galactose and mannose. The remaining part of the component was estimated as ligin because of the characteristic functional groups in IR and UV spectra. Concomitant treatment of HHM 3-1 with known mitogens synergistically increased the proliferation of B-cells and T-cells.

• Journal of Microbiology and Biotechnology
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• v.16 no.4
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• pp.569-575
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• 2006

The 530 stem-loop is a 46 nucleotide stem-loop structure found in all small-subunit ribosomal RNAs. Phylogenetic and mutational studies by others suggest the requirement for Watson-Crick interactions between the nucleotides 505-507 and 524-526 (530 pseudoknot), which are highly conserved. To examine the nature and functional significance of these interactions, a random mutagenesis experiment was conducted in which the nucleotides in the proposed pseudoknot were simultaneously mutated and functional mutants were selected and analyzed. Genetic analysis revealed that the particular nucleotide present at each position except 524 was not exclusively critical to the selection of functional mutants. It also indicated that basepairing interactions between the positions 505-507 and 524-526 were required for ribosomal function, and much weaker base-pairing interactions than those of the wild-type also allowed high ribosomal function. Our results support the hypothesis that the 530 pseudoknot structure may undergo a 'conformational switch' between folded and unfolded states during certain stages of the protein synthesis process by interacting with other ligands present in its environment.

• Journal of Microbiology and Biotechnology
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• v.22 no.12
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• pp.1790-1794
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• 2012

Recently, it has been suggested that $p27^{Kip1}$, the cell cycle regulatory protein, plays a pivotal role in the progression of normal differentiation in murine embryonic stem (mES) cells. In the current study, we investigated the role of $p27^{Kip1}$ in the regulation of differentiation and apoptotic induction using Western blotting, quantitative real-time RT-PCR, and small interfering RNA (siRNA) assays and confocal laser scanning microscopic analysis of H9 human ES (hES) cells and H9-derived embryoid bodies (EBs) grown for 10 ($EB_{10}$) and 20 days ($EB_{20}$). Our results demonstrate that the proteins $p27^{Kip1}$ and cyclin D3 are strongly associated with cellular differentiation, and, for the first time, show that up-regulation of $p27^{Kip1}$ protects hES cells from inducing differentiation-associated and caspase 3-dependent apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.35-42
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• 2015

In cardiovascular disorders, understanding of endothelial cell (EC) function is essential to elucidate the disease mechanism. Although the mouse model has many advantages for in vivo and in vitro research, efficient procedures for the isolation and propagation of primary mouse EC have been problematic. We describe a high yield process for isolation and in vitro culture of primary EC from mouse arteries (aorta, braches of superior mesenteric artery, and cerebral arteries from the circle of Willis). Mouse arteries were carefully dissected without damage under a light microscope, and small pieces of the vessels were transferred on/in a Matrigel matrix enriched with endothelial growth supplement. Primary cells that proliferated in Matrigel were propagated in advanced DMEM with fetal calf serum or platelet-derived serum, EC growth supplement, and heparin. To improve the purity of the cell culture, we applied shearing stress and anti-fibroblast antibody. EC were characterized by a monolayer cobble stone appearance, positive staining with acetylated low density lipoprotein labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate, RT-PCR using primers for von-Willebrand factor, and determination of the protein level endothelial nitric oxide synthase. Our simple, efficient method would facilitate in vitro functional investigations of EC from mouse vessels.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.487-498
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• 2016

Leptin, an adipokine predominantly produced from adipose tissue, is well known to induce tumor growth. However, underlying molecular mechanisms are not established yet. While p53 has long been well recognized as a potent tumor suppressor gene, accumulating evidence has also indicated its potential role in growth and survival of cancer cells depending on experimental environments. In the present study, we examined if p53 signaling is implicated in leptin-induced growth of cancer cells. Herein, we demonstrated that leptin treatment significantly increased p53 protein expression in both hepatic (HepG2) and breast (MCF-7) cancer cells without significant effect on mRNA expression. Enhanced p53 expression by leptin was mediated via modulation of ubiquitination, in particular ubiquitin specific protease 2 (USP2)-dependent manner. Furthermore, gene silencing of p53 by small interfering RNA (siRNA) suppressed leptin-induced growth of hepatic and breast cancer cells, indicating the role of p53 signaling in tumor growth by leptin. In addition, we also showed that knockdown of p53 restored suppression of caspase-3 activity by leptin through modulating Bax expression and prevented leptin-induced cell cycle progression, implying the involvement of p53 signaling in the regulation of both apoptosis and cell cycle progression in cancer cells treated with leptin. Taken together, the results in the present study demonstrated the potential role of p53 signaling in leptin-induced tumor growth.

• Korean Journal of Poultry Science
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• v.27 no.2
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• pp.133-153
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• 2000

The egg's interior quality is one of the most important criteria for commercial producers and consumers. Internal quality is complex, including aesthetic factors such as taste, freshness, nutritional and processing values, and the genetic influences upon these upon these factors ranges from none to considerable. The rate of cholesterol synthesis in the hen is very high compared to other animals and humans. Genetic selection, diet drugs and other chemicals can alter cholesterol concentration in the plasma of laying hen, but attempts to manipulate the cholesterol concentration in the egg yolk are generally unsuccessful since the cholesterol can only be changed to a small extent. Factors which may affect the degree of pigmentation of the yolk include the type of xanthophyll and its concentration in the feed, the feed composition, and the health of the hen. Several feed ingredients interact with carotenoid pigment to improve or reduce their deposition rates in yolks. Egg weight is determined by genetics, body size prior to first egg housing density, environmental temperature, lighting program, total feed consumption, calcium, phosphorus, niacin, water, methionine, total sulfur amino acids, energy, linoleic acid, fat and protein levels. Eggs need to be promote levels. Eggs need to be promoted a versatile commodity and new processed egg items need to be developed. Organic eggs are laid by hens which were raised in chemical and drug frdd environments. There are still difficulties in producing these eggs due to the availability of organic poultry feeds and cost of organic grains.

• Journal of Microbiology
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• v.43 no.5
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• pp.398-405
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• 2005

Polyamines such as putrescine are small, ubiquitous polycationic molecules that are required for optimal growth of eukaryotic and prokaryotic cells. These molecules have diverse effects on cell physiology and their intracellular content is regulated by de novo synthesis and uptake from the environment. The studies presented here examined the structure of a putative polyamine transporter (Pot) operon in Streptococcus pneumoniae (pneumococcus) and growth of pneumococci in medium containing putrescine substituted for choline. RT-PCR experiments demonstrated that the four genes encoding the Pot system are co-transcribed with murB, a gene involved in an intermediary step of peptidoglycan synthesis. Pneumococci grown in chemically-defined media (CDM) containing putrescine without choline enter logarithmic phase growth after 36-48 hs. However, culture density at stationary phase eventually reaches that of choline-containing medium. Cells grown in CDM-putrescine formed abnormally elongated chains in which the daughter cells failed to separate and the choline-binding protein PspA was no longer cell-associated. Experiments with CDM containing radiolabeled putrescine demonstrated that pneumococci concentrate this polyamine in cell walls. These data suggest that pneumococci can replicate without choline if putrescine is available and this polyamine may substitute for aminoalcohols in the cell wall teichoic acids.