• Molecules and Cells
• /
• v.24 no.2
• /
• pp.210-214
• /
• 2007

The 90-kDa heat shock protein (HSP90) normally functions as a molecular chaperone participating in folding and stabilizing newly synthesized proteins, and refolding denatured proteins. The HSP90 inhibitor geldanamycin (GA) occupies the ATP/ADP binding pocket of HSP90 so inhibits its chaperone activity and causes subsequent degradation of HSP90 client proteins by proteasomes. Here we show that GA reduces the level of endogenous c-Jun in human embryonic kidney 293 (HEK293) cells in a time and dose dependent manner, and that this decrease can be reversed by transfection of HSP90 plasmids. Transfection of HSP90 plasmids in the absence of GA increases the level of endogenous c-Jun protein, but has no obvious affect on c-Jun mRNA levels. We also showed that HSP90 prolongs the half-life of c-Jun by stabilizing the protein; the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) blocks the degradation of c-Jun promoted by GA. Transfection of HSP90 plasmids did not obviously alter phosphorylation of c-Jun, and a Jun-2 luciferase activity assay indicated that over-expression of HSP90 elevated the total protein activity of c-Jun in HEK293 cells. All our evidence indicates that HSP90 stabilizes c-Jun protein, and so increases the total activity of c-Jun in HEK293 cells.

• BMB Reports
• /
• v.45 no.2
• /
• pp.120-125
• /
• 2012

We have developed a biologist-friendly, Java GUI application (GoBean) for GO term enrichment analysis. It was designed to be a comprehensive and flexible GUI tool for GO term enrichment analysis, combining the merits of other programs and incorporating extensive graphic exploration of enrichment results. An intuitive user interface with multiple panels allows for extensive visual scrutiny of analysis results. The program includes many essential and useful features, such as enrichment analysis algorithms, multiple test correction methods, and versatile filtering of enriched GO terms for more focused analyses. A unique graphic interface reflecting the GO tree structure was devised to facilitate comparisons of multiple GO analysis results, which can provide valuable insights for biological interpretation. Additional features to enhance user convenience include built in ID conversion, evidence code-based gene-GO association filtering, set operations of gene lists and enriched GO terms, and user -provided data files. It is available at http://neon.gachon.ac.kr/GoBean/.

• Molecules and Cells
• /
• v.40 no.9
• /
• pp.613-620
• /
• 2017

The most common form of senile dementia is Alzheimer's disease (AD), which is characterized by the extracellular deposition of amyloid ${\beta}-peptide$ ($A{\beta}$) plaques and the intracellular formation of neurofibrillary tangles (NFTs) in the cerebral cortex. Tau abnormalities are commonly observed in many neurodegenerative diseases including AD, Parkinson's disease, and Pick's disease. Interestingly, tau-mediated formation of NFTs in AD brains shows better correlation with cognitive impairment than $A{\beta}$ plaque accumulation; pathological tau alone is sufficient to elicit frontotemporal dementia, but it does not cause AD. A growing amount of evidence suggests that soluble $A{\beta}$ oligomers in concert with hyperphosphorylated tau (pTau) serve as the major pathogenic drivers of neurodegeneration in AD. Increased $A{\beta}$ oligomers trigger neuronal dysfunction and network alternations in learning and memory circuitry prior to clinical onset of AD, leading to cognitive decline. Furthermore, accumulated damage to mitochondria in the course of aging, which is the best-known nongenetic risk factor for AD, may collaborate with soluble $A{\beta}$ and pTau to induce synapse loss and cognitive impairment in AD. In this review, I summarize and discuss the current knowledge of the molecular and cellular biology of AD and also the mechanisms that underlie $A{\beta}-mediated$ neurodegeneration.

• Journal of Ecology and Environment
• /
• v.31 no.1
• /
• pp.75-81
• /
• 2008

Rates of molecular evolution are known to vary widely among taxonomic groups. A number of studies, examining various taxonomic groups, have indicated that body size is negatively and clutch size is positively correlated with the rates of nucleotide substitutions among vertebrate species. Generally, either smaller body mass or larger clutch size is associated with shorter generation times and higher metabolic rates. However, this generality is subject to ongoing debate, and large-scale comparative studies of species below the Order level are lacking. In this study, phylogenetically independent methods were used to test for relationships between rates of the mitochondrial cytochrome b evolution and a range of life history traits, such as body mass and clutch size in the Order Galliformes. This analysis included data from 67 species of Galliformes birds and 2 outgroup species in Anseriformes. In contrast to previous studies, taxa were limited to within-Order level, not to Class or higher. I found no evidence to support an effect of life history traits on the rate of molecular evolution within the Galliformes. These results suggest that such relationship may be too weak to be observed in comparisons of closely related species or may not be a general pattern that is applicable to all nucleotide sequences or all taxonomic groups.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.12
• /
• pp.4803-4812
• /
• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• BMB Reports
• /
• v.41 no.9
• /
• pp.678-683
• /
• 2008

The initial step during assembly of the hepatitis A virus particle is driven by domain 2A of P1-2A, which is the precursor of the structural proteins. The proteolytic removal of 2A from particulate VP1-2A by an as yet unknown host enzyme presumably terminates viral morphogenesis. Using a genetic approach, we show that a basic amino acid residue at the C-terminus of VP1 is required for efficient particle assembly and that host proteases trypsin and cathepsin L remove 2A from hepatitis A virus particles in vitro. Analyses of insertion mutants in the C-terminus of 2A reveal that this part of 2A is important for liberation of P1-2A from the polyprotein. The data provide the first evidence that the VP1/2A junction is involved in both viral particle assembly and maturation and, therefore, seems to coordinate the first and last steps in viral morphogenesis.

• The Bulletin of The Korean Astronomical Society
• /
• v.36 no.2
• /
• pp.117.2-117.2
• /
• 2011

We probe 12CO J=2-1 and 13CO J=1-0 properties of a Virgo disk galaxy, NGC 4402 which is located near the cluster center. Our goal is to study the impact of intra cluster medium (ICM) on the molecular gas of a galaxy in the cluster environment. It has been believed that cluster galaxies are deficient in atomic hydrogen gas (HI gas) compared to their field counterparts and now there is much evidence that low density ISM can be easily removed by ram pressure caused by ICM wind. Meanwhile, no significant molecular gas deficiency of the cluster galaxy population has been found yet they show overall lower star formation rate than galaxies in the field, and it is still controversy whether dense ISM can be also stripped by the ICM wind or not. NGC 4402 with truncated HI disk($D_{HI}/D_{opt}$ ~ 0.75 and only 36%of HI gas compare to field galaxies of a similar size) and a disturbed gas morphology, appears to have strong ongoing ram pressure. Using high resolution 12 and 13CO data of NGC 4402 from a Sub Millimeter Array (SMA), we probe the molecular gas properties under strong ICM pressure. We discuss how its star formation activity and hence the global color of NGC4402 would be changed in the future.

• BMB Reports
• /
• v.38 no.3
• /
• pp.334-342
• /
• 2005

Recently, the existence of T cells with dual T cell receptor (TCR) in the immune system is generally accepted, while it has been controversial whether signals through one TCR would affect the functions of the other. In this study T cells expressing two different TCR were obtained from cross-hybrids of LCMV and AND TCR transgenic mice specific for the gp33 and peptide fragment of PCC (fPCC), respectively. Peptide stimulation demonstrated that the dual TCR T cells functioned independently in an antigen-specific manner. To examine whether the tolerance targeted for the one TCR affects the responsiveness of the other, the cross-hybrids were treated with gp33. Although T cells from F1 mice were rendered anergenic to gp33, no functional changes to fPCC were observed in terms of cellular proliferation and IL-2 secretion, suggesting that the dual TCR T cells remained reactive to fPCC. We therefore propose that signaling through the TCR is receptor-specific and 'negative dominance' of one TCR by tolerance induction is not applicable in this dual TCR system.

• BMB Reports
• /
• v.41 no.12
• /
• pp.881-885
• /
• 2008

Protein phosphatase 1 consists of a secondary structure arrangement, conserved in the serine/threonine protein phosphatase gene family, flanked by nonconserved N-terminal and C-terminal domains. The deletion mutant of PP1 with the 8 nonconserved N-terminal residues removed was designated PP1-(9-330). PP1-(9-330) had a higher activity and affinity than PP1 when assayed against four different substrates, and it also demonstrated a 6-fold higher sensitivity to the inhibitor okadaic acid. This suggested that the N-terminal domain suppresed the activity of PP1 and interfered with its inhibition by okadaic acid. The ANS fluorescence intensity of PP1-(9-330) was greater than that of PP1, which implies that the hydrophobic groove running from active site in the truncated PP1 was more hydrophobic than in PP1. Our findings provide evidence that the nonconserved N-terminus of PP1 functions as an important regulatory domain that influences the active site and its pertinent properties.

• Publications of The Korean Astronomical Society
• /
• v.30 no.2
• /
• pp.75-78
• /
• 2015

A growing body of evidence has been supporting the existence of so-called "dark molecular gas" (DMG), which is invisible in the most common tracer of molecular gas, i.e., CO rotational emission. DMG is believed to be the main gas component of the intermediate extinction region from Av~0.05-2, roughly corresponding to the self-shielding threshold of $H_2$ and $^{13}CO$. To quantify DMG relative to $H{\small{I}}$ and CO, we are pursuing three observational techniques; $H{\small{I}}$ self-absorption, OH absorption, and THz $C^+$ emission. In this paper, we focus on preliminary results from a CO and OH absorption survey of DMG candidates. Our analysis shows that the OH excitation temperature is close to that of the Galactic continuum background and that OH is a good DMG tracer co-existing with molecular hydrogen in regions without CO. Through systematic "absorption mapping" by the Square Kilometer Array (SKA) and ALMA, we will have unprecedented, comprehensive knowledge of the ISM components including DMG in terms of their temperature and density, which will impact our understanding of galaxy evolution and star formation profoundly.