• BMB Reports
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• v.52 no.2
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• pp.113-118
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• 2019

The small ubiquitin-related modification molecule (SUMO), one of the post-translational modification molecules, is involved in a variety of cellular functions where it regulates protein activity and stability, transcription, and cell cycling. Modulation of protein SUMOylation or deSUMOylation modification has been associated with regulation of carcinogenesis in breast cancer. In the dynamic processes of SUMOylation and deSUMOylation in a variety of cancers, SUMO proteases (SENPs), reverse SUMOylation by isopeptidase activity and SENPs are mostly elevated, and are related to poor patient prognosis. Although underlying mechanisms have been suggested for how SENPs participate in breast cancer tumorigenesis, such as through regulation of target protein transactivation, cancer cell survival, cell cycle, or other post-translational modification-related machinery recruitment, the effect of SENP isoform-specific inhibitors on the progression of breast cancer have not been well evaluated. This review will introduce the functions of SENP1 and SENP2 and the underlying signaling pathways in breast cancer for use in discovery of new biomarkers for diagnosis or therapeutic targets for treatment.

• Bulletin of the Korean Chemical Society
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• v.10 no.3
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• pp.223-226
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• 1989

The chemical reactivity of 5,7-dimethoxycoumarine with adenosine has been calculated by the frontier electron and PPP-Cl MO methods. Results suggest that the major reactivity of the 5,7-dimethoxycoumarin is highest at the carbon-4 (position 4), whereas the electrophilic reactivity is generally spread all over the 5,7-dimethoxycoumarin molecule. These results are consistent with the experimental photoaddition reaction products. The small change of bond orders on excitation does not give enough reactivity to triplet states or the efficient intersystem crossing from $T_1\;to\;S_0$ inhibits photoaddition of 5,7-dimethoxycoumarine to adenosine. Although the relative intensity of the singlet band appears to be considerably higher than the triplet band intensity, its integrated intensity, i.e. oscillator strength, is comparable to that of the 5,7-dimethoxycoumarin and adenosine bands.

• Bulletin of the Korean Chemical Society
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• v.6 no.5
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• pp.309-311
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• 1985

When a molecule is perturbed by an external field, the perturbed moecue can be described as a doubly perturbed system. Hartree-Fock operator in the absence of the field is the zeroth order Hamiltonian, and a correlation operator and the external field operator are perturbations. The effective Hamiltonian, which is a projection of the total Hamiltonian onto a small finite subspace (usually a valence space), has been formally derived. The influence of the external field to the molecular Hamiltonian itself has been examined within an effective Hamiltonian framework. The first order effective expectation values, for instance electromagnetic transition amplitudes, between valence states are found to be easily calculated - by simply taking matrix elements of the effective external field operator. Implications of the terms in perturbation expansion are discussed.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.133.1-133.1
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• 2003

Cathepsin K (CK) is a cysteine protease that plays a major and essential role in osteoclast-mediated degradation of collagen matrix of bone. Its tissue-limited distribution and pivotal contribution to bone resorption meet the requirements as the potential therapeutic target of the disease with excessive bone loss such as osteoporosis. In a search for potent CK inhibitors. we found OST-5440 that effectively inhibited bone resorption in vivo as well as in vitro. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.233.1-233.1
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• 2003

Interleukin (IL)-5 appears to be one of the main proinflammatory mediators among a growing number of cytokines and chemokines that induce eosinophilic inflammation. Sophoricoside and their analogs isolated from Sophora japonica show relatively potent inhibitory activity of interleukin (IL)-5 as a small molecule. Initial attempt to identify the structural requirement of this isoflavonone led to find new chalcones to exhibit the inhibitory activity of IL -5. (omitted)

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.262-265
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• 2024

• Molecules and Cells
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• v.43 no.6
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• pp.517-529
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• 2020

Carboxyl-terminal binding proteins (CtBPs) are transcription regulators that control gene expression in multiple cellular processes. Our recent findings indicated that overexpression of CtBP2 caused the repression of multiple bone development and differentiation genes, resulting in atrophic nonunion. Therefore, disrupting the CtBP2-associated transcriptional complex with small molecules may be an effective strategy to prevent nonunion. In the present study, we developed an in vitro screening system in yeast cells to identify small molecules capable of disrupting the CtBP2-p300 interaction. Herein, we focus our studies on revealing the in vitro and in vivo effects of a small molecule NSM00158, which showed the strongest inhibition of the CtBP2-p300 interaction in vitro. Our results indicated that NSM00158 could specifically disrupt CtBP2 function and cause the disassociation of the CtBP2-p300-Runx2 complex. The impairment of this complex led to failed binding of Runx2 to its downstream targets, causing their upregulation. Using a mouse fracture model, we evaluated the in vivo effect of NSM00158 on preventing nonunion. Consistent with the in vitro results, the NSM00158 treatment resulted in the upregulation of Runx2 downstream targets. Importantly, we found that the administration of NSM00158 could prevent the occurrence of nonunion. Our results suggest that NSM00158 represents a new potential compound to prevent the occurrence of nonunion by disrupting CtBP2 function and impairing the assembly of the CtBP2-p300-Runx2 transcriptional complex.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.34.1-34.15
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• 2023

Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.

• Journal of Life Science
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• v.23 no.9
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• pp.1118-1125
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• 2013

Naringenin, a naturally occurring citrus flavonone, is a potentially valuable candidate for cancer chemotherapy. However, the cellular and molecular mechanisms responsible for its anticancer activity are largely unknown. In the present study, we attempted to elucidate the mechanisms responsible for naringenin-induced apoptosis in human leukemic U937 cells. We found that naringenin markedly inhibited the growth of U937 cells by decreasing cell proliferation and inducing apoptosis, which was associated with the activation of caspases. A pan-caspase inhibitor, z-VAD-fmk, significantly inhibited naringenin-induced U937 cell apoptosis, indicating that caspases are key regulators of apoptosis in response to naringenin in U937 cells. Although the levels of antiapoptotic Bcl-2 and proapoptotic Bax proteins remained unchanged in naringenin-treated U937 cells, Bcl-2 overexpression attenuated naringenin-induced apoptosis. Furthermore, combined treatment with naringenin and HA14-1, a small-molecule Bcl-2 inhibitor, effectively increased the apoptosis through enhancement of XIAP down-regulation, Bid cleavage, and caspase activation, suggesting that the synergistic effect was at least partially mediated through the death receptor-mediated apoptosis pathway.

• Journal of Microbiology and Biotechnology
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• v.27 no.3
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• pp.460-470
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• 2017

Mussels are major fouling organisms causing serious technical and economic problems. In this study, antifouling activity towards mussel was found in three compounds isolated from a marine bacterium associated with the sea anemone Haliplanella sp. This bacterial strain, called PE2, was identified as Vibrio alginolyticus using morphology, biochemical tests, and phylogenetic analysis based on sequences of 16S rRNA and four housekeeping genes (rpoD, gyrB, rctB, and toxR). Three small-molecule compounds (indole, 3-formylindole, and cyclo (Pro-Leu)) were purified from the ethyl acetate extract of V. alginolyticus PE2 using column chromatography techniques. They all significantly inhibited byssal thread production of the green mussel Perna viridis, with $EC_{50}$ values of $24.45{\mu}g/ml$ for indole, $50.07{\mu}g/ml$ for 3-formylindole, and $49.24{\mu}g/ml$ for cyclo (Pro-Leu). Previous research on the antifouling activity of metabolites from marine bacteria towards mussels is scarce. Indole, 3-formylindole and cyclo (Pro-Leu) also exhibited antifouling activity against settlement of the barnacle Balanus albicostatus ($EC_{50}$ values of 8.84, 0.43, and $11.35{\mu}g/ml$, respectively) and the marine bacterium Pseudomonas sp. ($EC_{50}$ values of 42.68, 69.68, and $39.05{\mu}g/ml$, respectively). These results suggested that the three compounds are potentially useful for environmentally friendly mussel control and/or the development of new antifouling additives that are effective against several biofoulers.