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CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3
Seo, Jinho,Lee, Eun-Woo,Sung, Hyerim,Seong, Daehyeon,Dondelinger, Yves,Shin, Jihye,Jeong, Manhyung,Lee, Hae-Kyung,Kim, Jung-Hoon,Han, Su Yeon,Lee, Cheolju,Seong, Je Kyung,Vandenabeele, Peter,Song, Jae Nature Publishing Group 2016 NATURE CELL BIOLOGY Vol. No.
<P>Receptor-interacting protein kinase 3 (RIPK3) functions as a key regulator of necroptosis. Here, we report that the RIPK3 expression level is negatively regulated by CHIP (carboxyl terminus of Hsp70-interacting protein; also known as STUB1) E3 ligase-mediated ubiquitylation. Chip(-/-) mouse embryonic fibroblasts and CHIP-depleted L929 and HT-29 cells exhibited higher levels of RIPK3 expression, resulting in increased sensitivity to necroptosis induced by TNF (also known as TNF alpha). These phenomena are due to the CHIP-mediated ubiquitylation of RIPK3, which leads to its lysosomal degradation. Interestingly, RIPK1 expression is also negatively regulated by CHIP-mediated ubiquitylation, validating the major role of CHIP in necrosome formation and sensitivity to TNF-mediated necroptosis. Chip(-/-) mice (C57BL/6) exhibit inflammation in the thymus and massive cell death and disintegration in the small intestinal tract, and die within a few weeks after birth. These phenotypes are rescued by crossing with Ripk3(-/-) mice. These results imply that CHIP is a bona fide negative regulator of the RIPK1-RIPK3 necrosome formation leading to desensitization of TNF-mediated necroptosis.</P>
Yu, Mi Kyung,Park, Jinho,Jeong, Yong Yeon,Moon, Woo Kyung,Jon, Sangyong IOP Pub 2010 Nanotechnology Vol.21 No.41
<P>We report multifunctional nanoparticles that are capable of cancer targeting and simultaneous cancer imaging and therapy. The nanoparticles are composed of cyclic arginine–glycine–aspartic acid (cRGD) peptide ligand bioconjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) that enable loading of the anticancer drug doxorubicin (Dox). The cyclic RGD-conjugated TCL-SPION (cRGD_TCL-SPION) had a mean hydrodynamic size of 34 ± 8 nm with approximately 0.39 wt% of cyclic RGD attached to the surface of the nanoparticles. The cRGD_TCL-SPION exhibited preferential binding towards target cancer cells (U87MG, integrin α<SUB>v</SUB>β<SUB>3</SUB> +) when analyzed by <I>T</I><SUB>2</SUB>-weighted magnetic resonance (MR) imaging. When Dox was loaded onto the polymeric coating layers of cRGD_TCL-SPION via ionic interaction, the resulting Dox-loaded cRGD_TCL-SPION (Dox@cRGD_TCL-SPION) showed much higher cytotoxicity in U87MG cells than Dox@TCL-SPION lacking cRGD (IC<SUB>50</SUB> value of 0.02 µM versus 0.12 µM). These results suggest that Dox@cRGD_TCL-SPION has potential for use as an integrin-targeted, combined imaging and therapeutic agent. </P>
Sung-Min Lee,Do Kyung Hong,Jongseong Park,Jinho Lee,Sei-Heon Jang,ChangWoo Lee 한국응용곤충학회 2015 한국응용곤충학회 학술대회논문집 Vol.2015 No.04
The pine wilt disease that blocks the path for water and nutrition in pine trees is caused by the nematode, Bursaphelenchus xylophilus (Nematoda: Aphelenchoididae). The nematode relies on the longhorn pine sawyer beetle Monochamus alternatus and Monochamus saltuaris (Coleoptera: Cerambycidae) as vectors. Recently, 2-(undecyloxy)ethanol was identified as a male-produced aggregation pheromone of Monochamus species. In this study, we investigated the effect of 2-(undecyloxy) ethanol along with host plant volatiles -pinene and ethanol on attracting M. alternatus at a pine forest in Pohang, Korea from May, 2014 to July, 2014. To sustain the volatility of 2-(undecyloxy)ethanol and host plant volatiles, a superabsorbent polymer based on polyacrylic acids and water were added to the pheromone mixture. A total of 46 M. alternatus were collected from two field bioassays. Our results indicate that 2-(undecyloxy)ethanol is effective in attracting M. alternatus in Korea. Our study suggests that the aggregation pheromone could be used for detection and population monitoring of the beetles as well as for the effective mass trapping in outbreak situations.
Jong-Wook Lee(Jong-Wook Lee),Hyeon-Soo Ahn(Hyeon-Soo Ahn),Jinho Chang(Jinho Chang),Hye-Young Kang(Hye-Young Kang),Dong-Jin Chang(Dong-Jin Chang),Jae Kyung Suh(Jae Kyung Suh),Hankil Lee(Hankil Lee) 대한안과학회 2022 Korean Journal of Ophthalmology Vol.36 No.5
Purpose: Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma. Methods: We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy. Results: Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each. Conclusions: Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.
Kyung Hee Park,Jinho Byun 한국재무학회 2020 한국재무학회 학술대회 Vol.2020 No.11
As can be seen in the Fourth Industrial Revolution, investment in intangible assets is becoming increasingly important. Against the backdrop of this corporate environment, we examined how overconfident CEOs invest in intangible assets and tangible assets. We measured CEOs’ overconfidence through the manager's narrative in 10-K, and identified using textual analysis. The results of this study are as follows. First, as CEOs' optimism increases, investment in tangible and intangible assets increases. Second, overconfident CEOs reduce investment in intangible assets. Third, under the constraints of cash flow, overconfidence CEOs partially increase intangible investment. Fourth, increased intangible investment under cash flow constraints has a positive relationship with long-term performance of firm. This study has the following implications. Since most investments in intangible assets are not accounted for as assets on the balance sheet and are treated as expenses, overconfident managers seem to reduce this. In addition, long-term performance was found to be good if overconfident managers invested in intangible assets even under cash flow constraints. It is interpreted that this is because the intangible assets invested in spite of cash flow constraints act as a core competency for companies.
The Effect of the Refixing Option in Convertible Bond on Shareholders' Wealth
Jinho Byun,Kyung-Hee Park 한국재무학회 2017 한국재무학회 학술대회 Vol.2017 No.05
In the Korean convertible bond market, there is a refix option that allows for the adjustment of the conversion price according to a fall in stock prices. This is a unique system in Korea. In this study, we look into how a refix clause of convertible bonds impacts the wealth of shareholders, and analyzed whether the aim of this clause, which is to protect investors, is valid. The refix option is a system where the conversion price of convertible bonds is pulled down when the stock price falls after the security’s issuance. For investors, this could be beneficial, as the number of stocks one can receive increases despite a fall in stock prices. However, for shareholders, it can mean dangers of stock dilution, resulting from an increase in the number of issued stocks. This paper analyzes the impact of refix clauses on shareholders, by studying the existence or nonexistence of refix effect and the announcement effect of refix clauses. Study results are as follows: First, a higher negative market response was observed after an announcement to issue a convertible bond with a refix clause. Second, the market also responded negatively even at the point in time that a refix in price actually occurs, which suggests that “refixing” of convertible bonds undermines wealth of actual shareholders. Third, it was found that the announcement effect less negative as the share of the majority shareholder goes higher, which points to a correlation between the share of the majority shareholder and the refix clause. Compared to the United States and other developed countries, the current refix clause in Korea seems to excessively focus on the protection of convertible bond investors, and there seems to be room for improvements in the future.
오진호(Jinho Oh),김현동(Hyun Dong Kim),이정언(Jung-Eon Lee),양준환(Jun Hwan Yang),김경천(Kyung Chun Kim) 한국가시화정보학회 2021 한국가시화정보학회지 Vol.19 No.3
An experiment to visualize fine dust captured by FOG droplet is conducted. Coal dust with 23.56 MMD (Mean Median Diameter) and water with 17.02 MMD is used as fine dust and FOG droplet. Long distance microscope and high-speed camera are used to capture the images of micro-scale particles sprinkled by acrylic duct. After measuring and comparing the size of the coal dust and FOG droplet to MMD, process to seize the coal dust with FOG droplet is recorded in 2 conditions: Fixed and Floated coal dust in the floated FOG droplet flow. In both conditions, a coal dust particle is collided and captured by a FOG droplet particle. A FOG droplet particle attached at the surface of the coal dust particle does not break and remains spherical shape due to surface tension. Combined particles are rotated by momentum of the particle and fallen.