• Molecules and Cells
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• v.40 no.7
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• pp.441-449
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• 2017

Proteolysis in eukaryotic cells is mainly mediated by the ubiquitin (Ub)-proteasome system (UPS) and the autophagy-lysosome system (hereafter autophagy). The UPS is a selective proteolytic system in which substrates are recognized and tagged with ubiquitin for processive degradation by the proteasome. Autophagy is a bulk degradative system that uses lysosomal hydrolases to degrade proteins as well as various other cellular constituents. Since the inception of their discoveries, the UPS and autophagy were thought to be independent of each other in components, action mechanisms, and substrate selectivity. Recent studies suggest that cells operate a single proteolytic network comprising of the UPS and autophagy that share notable similarity in many aspects and functionally cooperate with each other to maintain proteostasis. In this review, we discuss the mechanisms underlying the crosstalk and interplay between the UPS and autophagy, with an emphasis on substrate selectivity and compensatory regulation under cellular stresses.

• The Journal of Korea Institute of Information, Electronics, and Communication Technology
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• v.1 no.2
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• pp.39-50
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• 2008

Developing computational methods for identifying cell cycle-regulated genes has been one of important topics in systems biology. Most of previous methods consider the periodic characteristics of expression signals to identify the cell cycle-regulated genes. However, we assume that cell cycle-regulated genes are relatively active having relatively many interactions with each other based on the underlying cellular network. Thus, we are motivated to apply the theory of multivariate phase synchronization to the cell cycle expression analysis. In this study, we apply the method known as "Self-Organizing Maps with statistical Phase Synchronization (SOMPS)", which is the combination of self-organizing map and multivariate phase synchronization, producing several subsets of genes that are expected to have interactions with each other in their subset (Kim, 2008). Our evaluation experiments show that the SOMPS algorithm is able to detect cell cycle-regulated genes as much as one of recently reported method that performs better than most existing methods.

• Molecules and Cells
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• v.37 no.3
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• pp.189-195
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• 2014

The NF-${\kappa}B$ pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF-${\kappa}B$ in cancer cells, recent findings postulate that NF-${\kappa}B$ participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-${\kappa}B$. In this review, we discuss implications of the NF-${\kappa}B$ signaling pathway in cancer. Particularly, we emphasize the connection of NF-${\kappa}B$ with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-${\kappa}B$ produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.

• BMB Reports
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• v.52 no.2
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• pp.109-110
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• 2019

Mitochondrial morphology is known to be continuously changing via fusion and fission, but it is unclear what the biological importance of this energy-consuming process is and how it develops. Several data have suggested that mitochondrial fission executed by Drp1 is necessary to select out a damaged spot from the interconnected mitochondrial network, but the precise mechanism for the recognition and isolation of a damaged sub-mitochondrial region during mitochondrial fission is yet unclear. Recently, Cho et al. found that the mitochondrial membrane potential (MMP) is transiently reduced by the physical interaction of Drp1 and mitochondrial Zinc transporter, Zip1, at the fission site prior to the typical mitochondrial division, and we found that this event is essential for a mitochondrial quality surveillance. In this review, Cho et al. discuss the role of a mitochondrial fission in the mitochondrial quality surveillance system.

• Molecules and Cells
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• v.42 no.9
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• pp.617-627
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• 2019

Brain organoids are an exciting new technology with the potential to significantly change our understanding of the development and disorders of the human brain. With step-by-step differentiation protocols, three-dimensional neural tissues are self-organized from pluripotent stem cells, and recapitulate the major millstones of human brain development in vitro. Recent studies have shown that brain organoids can mimic the spatiotemporal dynamicity of neurogenesis, the formation of regional neural circuitry, and the integration of glial cells into a neural network. This suggests that brain organoids could serve as a representative model system to study the human brain. In this review, we will overview the development of brain organoid technology, its current progress and applications, and future prospects of this technology.

• Development and Reproduction
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• v.23 no.1
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• pp.1-9
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• 2019

The ability of oocytes to undergo normal fertilization and embryo development is acquired during oocyte maturation which is transition from the germinal vesicle stage (GV), germinal vesicle breakdown (GVBD) to metaphase of meiosis II (MII). Part of this process includes redistribution of inositol 1, 4, 5-triphosphate receptor (IP3R), a predominant $Ca^{2+}$ channel on the endoplasmic reticulum membrane. Type 1 IP3R (IP3R1) is expressed in mouse oocytes dominantly. At GV stage, IP3R1 are arranged as a network throughout the cytoplasm with minute accumulation around the nucleus. At MII stage, IP3R1 diffuses to the entire cytoplasm in a more reticular manner, and obvious clusters of IP3R1 are observed at the cortex of the egg. This structural reorganization provides acquisition of $[Ca^{2+}]_i$ oscillatory activity during fertilization. In this review, general properties of IP3R1 in somatic cells and mammalian oocyte are introduced.

• Molecules and Cells
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• v.45 no.1
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• pp.6-15
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• 2022

Phase separation is a thermodynamic process leading to the formation of compositionally distinct phases. For the past few years, numerous works have shown that biomolecular phase separation serves as biogenesis mechanisms of diverse intracellular condensates, and aberrant phase transitions are associated with disease states such as neurodegenerative diseases and cancers. Condensates exhibit rich phase behaviors including multiphase internal structuring, noise buffering, and compositional tunability. Recent studies have begun to uncover how a network of intermolecular interactions can give rise to various biophysical features of condensates. Here, we review phase behaviors of biomolecules, particularly with regard to regular solution models of binary and ternary mixtures. We discuss how these theoretical frameworks explain many aspects of the assembly, composition, and miscibility of diverse biomolecular phases, and highlight how a model-based approach can help elucidate the detailed thermodynamic principle for multicomponent intracellular phase separation.

• BMB Reports
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• v.54 no.11
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• pp.569-574
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• 2021

Vascular calcification is the heterotopic accumulation of calcium phosphate salts in the vascular tissue and is highly correlated with increased cardiovascular morbidity and mortality. In this study, we found that the expression of neuromedin B (NMB) and NMB receptor is upregulated in phosphate-induced calcification of vascular smooth muscle cells (VSMCs). Silencing of NMB or treatment with NMB receptor antagonist, PD168368, inhibited the phosphate-induced osteogenic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling and VSMC apoptosis. PD168368 also attenuated the arterial calcification in cultured aortic rings and in a rat model of chronic kidney disease. The results of this study suggest that NMB-NMB receptor axis may have potential therapeutic value in the diagnosis and treatment of vascular calcification.

• Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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• 2022.05a
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• pp.216-217
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• 2022

Poisson-Boltzmann equation (PBD), which describes the effects of charges inside cells, plays important roles in various disciplinaries including biology. In this presentation, we introduce a ResNet based method to predict solution of PBE. First, we generate solutions of PBE based on FEM. Next, we train networks whose input shape includes location of charge and shape of cell and while output shape includes the electronic potential.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.9.1-9.15
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• 2023

Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8⁺ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8⁺ T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.