• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 58th Annual Meeting of The Korean Society of Pharmacology
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• pp.35-35
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• 2006

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.79-83
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• 2002

• 한국동물학회:학술대회논문집
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• 한국동물학회 1994년도 한국생물과학협회 학술발표대회
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• pp.158.1-158
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• 1994

• Bulletin of the Korean Chemical Society
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• 제34권8호
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• pp.2249-2250
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• 2013

• 대한약학회:학술대회논문집
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• 대한약학회 2005년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.217-217
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• 2005

• Toxicological Research
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• 제19권3호
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• pp.197-203
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• 2003

Apicidin, a histone-deacetylase inhibitor, has been successfully used to inhibit the growth of cancer cells. In this study, the apoptotic potential and mechanistic insights of apicidin were investigated in human myeloid leukemia U937 cells. Treatment of U937 cells with apicidin resulted in a decrease of cell viability with apoptotic characteristics, including chromatin condensation and ladder-pattern fragmentation of genomic DNA. Apicidin converted the procaspase-3 protease to catalytically active effector protease, resulting in subsequent cleavage of poly (ADP-ribose) polymerase (PARP) and inhibitor of caspase-activated deoxyribonuclease (ICAD). In addition, apicidin induced the activation of caspase-9 protease and the cytosolic release of mitochondrial cytochrome c with mitochon-drial membrane potential transition. Moreover, apicidin transiently increased the expression of Fas and Fas ligand proteins. Taken together, the results suggest that apicidin induces apoptosis of U937 cells through activation of intrinsic caspase cascades and Fas/FasL system with mitochondrial dysfunction.

• Bulletin of the Korean Chemical Society
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• 제33권2호
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• pp.535-540
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• 2012

A series of benzamide-based histone deacetylases (HDACs) inhibitors possessing N-(aminopyridine) residue as the zinc binding site of HDAC were synthesized and evaluated. Among these derivatives, compounds with N-(2-amino-4-pyridine) benzamide moiety have been found as the most potent ones. Moreover, introduction of appropriate substituents on the terminal aryl group acting as the surface-recognition domain could significantly improve the antiproliferative activity. In particular, the compound 4k possessed favorable pharmacokinetic characteristics and exhibited potent antitumor activity on xenograft model in mice at well tolerated doses, thus suggesting a good therapeutic index.

• BMB Reports
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• 제43권10호
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• pp.649-655
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• 2010

Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid $\beta$ protein (A$\beta$), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD.

• BMB Reports
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• 제28권2호
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• pp.143-148
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• 1995

In E. coli, chromosomal DNA associated with proteins is condensed into an organized structure known as nucleoid. Using a nitrocellulose filter binding assay to identify proteins forming nucleoid, a 21 kDa protein was purified from E. coli. The molecular weight of the purified protein was 21 kDa on SDS-polyactylamide gel electrophoresis and 24 kDa on gel permeation chromatography. A molecular weight of 21 kDa on SDS-polyacrylamide gel electrophoresis is unique among known proteins which are believed to be involved in the formation of nucleoid in E. coli. The 21 kDa protein nonspecifically binds to both double-stranded and single-stranded DNA. Sedimentation in a sucrose gradient revealed that the protein induced significant condensation of both supercoiled plasmid DNA and linear bacteriophage $\lambda$ DNA On the basis of quantitative Western-blot analysis, approximately 40,000 molecules of the protein were estimated to exist in an E. coli. The biochemical properties and cellular abundance of the 21 kDa protein suggest that this protein participates in the formation of nucleoid in E. coli.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.78-82
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• 2007

The proto-oncogene protein DEK is a nuclear binding phosphoprotein that has been associated with various human diseases including leukemia. Histone acetylation is an important post-translational modification which plays important role in transcriptional regulation. Auto-acetylation of histone acetyltransferase PCAF results in increment of its HAT activity and facilitation of its nuclear localization. In this study, we report that DEK inhibits PCAF auto-acetylation through direct interaction. The C-terminal acidic domains of DEK are responsible for the interaction with PCAF. Using confocal microscopy, we have shown that nuclear localization of PCAF is severely inhibited by DEK. Taken together, our results suggest that DEK may be involved in various cellular signal transduction pathways accommodated by PCAF through the regulation of PCAF auto-acetylation.