• Journal of the Korean Magnetic Resonance Society
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• v.19 no.2
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• pp.88-94
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• 2015

Bub1 is one of the spindle checkpoint proteins and plays a role in recruitment of the related proteins to kinetochore. Here, we studied the structural characteristic of the evolutionarily conserved 160 amino acid region in the N-terminus (hBub1 CD1), using Circular Dichroism (CD) and NMR. Our CD results showed that hBub1 CD1 is a highly helical protein and its structure was affected by pH: as pH was elevated to basic pH, the helical propensity increased. This could be related to the surface charge of the hBub1 CD1. However, the structural change did not largely depend on the salt concentration, though the thermal stability a little increased. The previous NMR analysis revealed that the hBub1 CD1 adopts eight helices, which is consistent with the CD result. Our result would be helpful for evaluating the molecular mechanism of the hBub1 CD1 and protein-protein interactions.

• Journal of Microbiology and Biotechnology
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• v.13 no.4
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• pp.624-627
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• 2003

Benzo[a]pyrene (B[a]P) is an environmental pollutant that has been implicated in carcinogenesis. Saccharomyces cerevisiae was treated with B[a]P, and the responses of its cytochrome P450 (CYP) enzyme and DNA-damage checkpoint genes were examined through gene expression profiles using a reverse transcription polymerase chain reaction (RT-PCR). The DNA-damage checkpoint genes tested were the chk1 and pds1 genes, involved in a metaphase arrest, the swi6 gene targeted by G1 arrest, the pol2 gene related to S phase arrest, and the cln2 gene encoding a cyclin protein, all of which are based on rad9 and rad24. Among these genes, no noticeable effect was found when the cells were exposed to various concentrations of B[a]P. However, the transcriptional activity of CYP51 was significantly different when the cells were exposed to B[a]P. Accordingly, the present results indicate that cytochrome P450 plays a more significant role than DNA-damage checkpoint genes in the response of S. cerevisiae to B[a]P.

• The Transactions of the Korea Information Processing Society
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• v.6 no.1
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• pp.216-224
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• 1999

In the paper we propose two recovery methods by adopting a rollback and/or roll-forward technique (S) to recover TMR failures in a TMR (structured ) system that is the simplest spatial redundancy. This technique is apparently effective to recovering TMR failures primarily caused by transient faults. The proposed policies carry out few reconfigurations at the cost of (minimal) time-overhead needed for those time-redundant schemes. The optimal checkpoint-interval vectors are derived for both methods through the likelihoods of all (possible) states of the system as well as the total execution-time. Consequently the effectiveness of our proposed policies is validated through certain numerical examples and simulations.

• Molecules and Cells
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• v.27 no.3
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• pp.359-363
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• 2009

Chfr, a checkpoint with FHA and RING finger domains, plays an important role in cell cycle progression and tumor suppression. Chfr possesses the E3 ubiquitin ligase activity and stimulates the formation of polyubiquitin chains by Ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins, including Plk1 and Aurora A. While Chfr is a nuclear protein that functions within the cell nucleus, how Chfr is localized in the nucleus has not been clearly demonstrated. Here, we show that nuclear localization of Chfr is mediated by nuclear localization signal (NLS) sequences. To reveal the signal sequences responsible for nuclear localization, a short lysine-rich stretch (KKK) at amino acid residues 257-259 was replaced with alanine, which completely abolished nuclear localization. Moreover, we show that nuclear localization of Chfr is essential for its checkpoint function but not for its stability. Thus, our results suggest that NLS-mediated nuclear localization of Chfr leads to its accumulation within the nucleus, which may be important in the regulation of Chfr activation and Chfr-mediated cellular processes, including cell cycle progression and tumor suppression.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.29-41
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• 2018

Lung cancer is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths worldwide. Although progress in the treatment of advanced non-small cell lung cancer (NSCLC) has been made over the past decade, the 5-year survival rate in patients with lung cancer remains only 10%-20%. Obviously, new therapeutic options are required for patients with advanced NSCLC and unmet medical needs. Cancer immunotherapy is an evolving treatment modality that uses a patient's own immune systems to fight cancer. Theoretically, cancer immunotherapy can result in long-term cancer remission and may not cause the same side effects as chemotherapy and radiation. Immunooncology has become an important focus of basic research as well as clinical trials for the treatment of NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer immunotherapy and they have become the standard of care for patients with advanced NSCLC. This review summarizes basic tumor immunology and the relevant clinical data on immunotherapeutic approaches, especially immune checkpoint inhibitors in NSCLC.

• BMB Reports
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• v.54 no.8
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• pp.431-436
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• 2021

In recent years, restoring anti-tumor immunity has garnered a growing interest in cancer treatment. As potential therapeutics, immune checkpoint inhibitors have demonstrated benefits in many clinical studies. Although various methods have been applied to suppress immune checkpoints to boost anti-tumor immunity, including the use of immune checkpoint inhibitors, there are still unmet clinical needs to improve the response rate of cancer treatment. Here, we show that acetate can suppress the expression of poliovirus receptor (PVR/CD155), a ligand for immune checkpoint, in colon cancer cells. We demonstrated that acetate treatment could enhance effector responses of CD8⁺ T cells by decreasing the expression of PVR/CD155 in cancer cells. We also found that acetate could reduce the expression of PVR/CD155 by deactivating the PI3K/AKT pathway. These results demonstrate that acetate-mediated expression of PVR/CD155 in cancer cells might potentiate the anti-tumor immunity in the microenvironment of cancer. Our findings indicate that maintaining particular acetate concentrations could be a complementary strategy in current cancer treatment.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.340-349
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• 2023

Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response.

• Mycobiology
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• v.51 no.2
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• pp.94-108
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• 2023

Termitomyces sp. that grow in symbiosis with fungus-farming Termites have medicinal properties. However, they are rare in nature, and their artificial culture is challenging. The expression of AXL receptor tyrosine kinase and immune checkpoint molecules favor the growth of cancer cells. The study evaluated the optimal conditions for the artificial culture of Termitomyces and their inhibitory activity on AXL and immune checkpoint molecules in lung adenocarcinoma and melanoma cell lines. The culture of 45 strains of Termitomyces was compared. Five strains with marked growth rates were selected. Four of the selected strains form a single cluster by sequence analysis. The mycelium of 4 selected strains produces more fungal mass in potato dextrose broth than in a mixed media. The bark was the most appropriate solid substrate for Termitomyces mycelia culture. The mycelium of all five selected strains showed a higher growth rate under normal CO₂ conditions. The culture broth, methanol, and ethyl acetate of one selected strain (T-120) inhibited the mRNA relative expression of AXL receptor tyrosine kinase and immune checkpoint molecules in cancer cell lines. Overall, these results suggest the potential usefulness of Termitomyces extracts as a coadjuvant therapy in malignant diseases.

• Journal of Digestive Cancer Research
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• v.10 no.2
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• pp.65-73
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• 2022

A breakthrough in immunotherapy has changed the outlook for metastatic colorectal cancer (mCRC) treatment as the immune surveillance evasion mechanism of tumor cells has been continuously elucidated. Immune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, and ipilimumab, which block immune checkpoint receptors or ligands have been approved for the treatment of mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC based on numerous clinical studies. However, 50% of dMMR/MSI-H mCRC and most mismatch repair proficient/microsatellite stable mCRC remained unresponsive to current immunotherapy. Clinical trials on combination therapy that adds various treatments, such as target agents, chemotherapy, or radiation therapy to ICI, have been actively conducted to overcome this immunotherapy limitation. Further studies on safety and efficacy are needed although several trials presented promising data. Additionally, dMMR/MSI-H, tumor mutation burden, and programmed cell death ligand-1 expression have been studied as biomarkers for predicting the treatment response to immunotherapy, but the discovery and validation of more sensitively predictable biomarkers remained necessary. Thus, this study aimed to review recent studies on immunotherapy in mCRC, summarize the efficacy and limitation of immunotherapy, and describe the biomarkers that predict treatment response.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.287-294
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• 2016

The effect of kaempferol (3,5,7,4-tetrahydroxyflavone), a flavonoid compound that was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G₂-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clones stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity and activation of the ATM/ATR-Chk1/Chk2 pathway, activating the phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), with resultant G₂-arrest of the cell cycle. Under these conditions, apoptotic events, including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9, -8, and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G₁ cells, were induced without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G₂-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA-damage-mediated G₂-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G₂-checkpoint activation, which caused not only G₂-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondria-dependent apoptotic events, including Bak and PUMA upregulation, Bak activation, Δψm loss, and caspase cascade activation.