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10. DOT1L is critical for adult vessel maintenance and functions

Author

Lee, HeeJi, primary, Han, Dong Wook, additional, La, Hyeonwoo, additional, Park, Chanhyeok, additional, Kang, Kiye, additional, Kwon, Ohbeom, additional, Uhm, Sang Jun, additional, Song, Hyuk, additional, Do, Jeong Tae, additional, Choi, Youngsok, additional, and Hong, Kwonho, additional

Published
2024
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13. Identification of plant compounds that disrupt the insect juvenile hormone receptor complex

Author

Lee, Seok-Hee, Oh, Hyun-Woo, Fang, Ying, An, Saes-Byeol, Park, Doo-Sang, Song, Hyuk-Hwan, Oh, Sei-Ryang, Kim, Soo-Young, Kim, Seonghyun, Kim, Namjung, Raikhel, Alexander S, Je, Yeon Ho, and Shin, Sang Woon

Subjects
Vector-Borne Diseases, Infectious Diseases, Animals, Diterpenes, Herbivory, Insect Proteins, Insecta, Juvenile Hormones, Larva, Lindera, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Solidago, Two-Hybrid System Techniques, juvenile hormone, receptor, endocrine disruptor
Abstract

Insects impact human health through vector-borne diseases and cause major economic losses by damaging crops and stored agricultural products. Insect-specific growth regulators represent attractive control agents because of their safety to the environment and humans. We identified plant compounds that serve as juvenile hormone antagonists (PJHANs). Using the yeast two-hybrid system transformed with the mosquito JH receptor as a reporter system, we demonstrate that PJHANs affect the JH receptor, methoprene-tolerant (Met), by disrupting its complex with CYCLE or FISC, formation of which is required for mediating JH action. We isolated five diterpene secondary metabolites with JH antagonist activity from two plants: Lindera erythrocarpa and Solidago serotina. They are effective in causing mortality of mosquito larvae at relatively low LD50 values. Topical application of two diterpenes caused reduction in the expression of Met target genes and retardation of follicle development in mosquito ovaries. Hence, the newly discovered PJHANs may lead to development of a new class of safe and effective pesticides.

Published
2015

17. INO80 function is required for mouse mammary gland development, but mutation alone may be insufficient for breast cancer

Author

Thang, Nguyen Xuan, primary, Han, Dong Wook, additional, Park, Chanhyeok, additional, Lee, Hyeonji, additional, La, Hyeonwoo, additional, Yoo, Seonho, additional, Lee, Heeji, additional, Uhm, Sang Jun, additional, Song, Hyuk, additional, Do, Jeong Tae, additional, Park, Kyoung Sik, additional, Choi, Youngsok, additional, and Hong, Kwonho, additional

Published
2023
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22. A mutagenic study of functional and structural aspects of rat insulin-like growth factor binding protein-5

Author

Song, Hyuk

Subjects
572.8, Apoptosis, Mammary epithelial cells
Abstract

On going research in our laboratory is focussed on the potential role of Insulin-like growth factor binding protein-5 (IGFBP-5) in apoptosis of mammary epithelial cells. In order to increase our understanding of IGFBP-5 functions, the work described below focussed on the relationship between the structure of the binding protein and its important molecular interactions. Using site-directed mutagenesis, we have mutated two highly conserved amino acids, Gly203 and Gln209 (G203K and Q209A respectively) within the basic amino acid rich region (201- 218) in the C-terminal domain of rat IGFBP-5. After analysis of binding activity using three different methods - IGF ligand blotting, IGF solution phase equilibrium binding and biosensor measurement - we have shown that the mutation of either of these two residues results in a reduction in affinity of the binding protein for both IGF-I and IGF-II by approximately ten-fold. Furthermore, mutation of both amino acids (G203K/Q209A, termed the Double mutant) had a cumulative effect and results in the complete ablation of IGF-I binding and a several thousand-fold reduction in IGF-II binding. This reduction in IGF binding affinity was comparable to that observed for the C-terminally truncated mutant BP550 (residues 1-168), which suggests that Gly203 and Gln209 may be the major determinants for IGF binding in the C-terminal domain. In addition, using heparin ligand blots, we confirm that mutation of basic residues within the C-terminal 201- 218 region (Hep- mutant: R201L, K202E, K206Q and R214A) results in major attenuation of heparin binding, whereas the G203K and Q209A single mutants and the Double mutant have no reduction in heparin binding. Therefore, our data suggests a potential overlap of heparin- and IGF- binding domains in the C-terminal region of IGFBP-5, and based on this, we discuss a potential model to explain the observed lower IGF binding affinity of ECM-bound IGFBP-5. In an attempt to assess the separate contribution of the N- and C-terminal domains to IGF binding, we also made four chimeric IGFBP cDNAs, BP552, BP522, BP255 and BP225, by switching domains between rat IGFBP-5 and rat IGFBP-2. We were consistently unable to detect expression of BP225 protein in the baculovirus/insect cell system, so this chimera had to be excluded from further study. Recognition of BP552 and BP522 proteins by both anti-rat IGFBP-5 and anti-rat IGFBP-2 antisera confirms their identity as chimeric proteins made up of domains from the native binding proteins, while BP255 was only recognised by the anti-rat IGFBP-5. The IGF binding properties of unpurified BP552, BP522 and BP255 proteins were assessed by IGF ligand blotting and IGF solution phase binding assays. These experiments demonstrated that BP552 and BP522 had comparable affinities with native IGFBP, whereas we were unable to detect any binding of BP255 to IGF-I by either technique, and only very weak interaction with IGF-II. Purified BP552 and BP522 were also tested by biosensor analysis, and data confirmed the results from the previous experiments. From this we can conclude that the N-terminal domain of IGFBP-5 can co-operate with the C-terminal domain of IGFBP-2 to produce a high affinity IGF binding species, irrespective of which central domain is present, whereas preliminary evidence would suggest that this cooperation may not occur between the N-terminal domain of IGFBP-2 and the C-terminal domain of lGFBP-5. In addition to IGF binding, the IGFBP-5 protein contains consensus heparin binding motifs in both its C-terminal and central domains, although only the C-terminal site was previously shown to be functional. Using heparin ligand blotting, it was found that the ability of BP552 and BP550 to bind to heparin was equivalent to that of WTIGFBP-5, whereas WTIGFBP-2 and BP522 failed to bind. These results demonstrate that an active heparin binding site in BP552 and BP550 is contained within the central domain of IGFBP-5, and that this site is only active in the absence of the carboxy-terminal domain. We subsequently mutated two basic amino acids (RI36A:R137A) in the central consensus binding sites between residues 132-140. This resulted in the loss of heparin binding for BP550, confirming the importance of these two basic amino acids in the central domain heparin binding activity. In light of these findings, we suggest that C-terminally truncated fragments of IGFBP-5 generated in vivo by proteolysis could retain heparin/extracellular matrix (ECM) binding properties. Finally, we propose that our various IGFBP-5 mutants described above provide an opportunity to test the structure-function relationships of this binding protein in an appropriate biological context.

Published
2001

31. Epigenetic priming by Dot1l in lymphatic endothelial progenitors ensures normal lymphatic development and function

Author

Yoo, Hyunjin, Lee, Young Jae, Park, Chanhyeok, Son, Dabin, Choi, Dong Yoon, Park, Ji-Hyun, Choi, Hee-Jin, La, Hyun Woo, Choi, Yun-Jung, Moon, Eun-Hye, Saur, Dieter, Chung, Hyung Min, Song, Hyuk, Do, Jeong Tae, Jang, Hoon, Lee, Dong Ryul, Park, Chankyu, Lee, Ok-Hee, Cho, Ssang-Goo, Hong, Seok-Ho, Kong, Gu, Kim, Jin-Hoi, Choi, Youngsok, and Hong, Kwonho

Published
2020
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47. The First Identification of Cryptosporidium parvum Virus-1 (CSpV1) in Hanwoo (Bos taurus coreanae) Calves in Korea.

Author

Chae, Jeong-Byoung, Shin, Seung-Uk, Kim, Serim, Jo, Young-Mi, Roh, Hyunsoo, Chae, Hansong, Kim, Won-Gyeong, Chae, Joon-Seok, Song, Hyuk, and Kang, Jung-Won

Subjects
CRYPTOSPORIDIUM, CRYPTOSPORIDIUM parvum, CATTLE, CALVES, DOUBLE-stranded RNA, POLYMERASE chain reaction
Abstract

Simple Summary: Cryptosporidium is a parasite that causes digestive diseases in cows, and a virus called Cryptosporidium parvum virus-1 (CSpV1) is associated with it. We investigated the presence and features of CSpV1 in diarrhea samples of Hanwoo calves (Korean indigenous cattle). Out of 140 samples, 70 were positive for Cryptosporidium and 70 were negative. CSpV1 was found in 20% of the samples, more commonly in those already positive for the parasite. This is the first study on CSpV1 in Korea, offering insights into the relationship between the parasite and virus in cows. Cryptosporidium is an obligate coccidian parasite that causes enteric diseases in bovine species. A double-stranded RNA virus associated with C. parvum oocysts, Cryptosporidium parvum virus-1 (CSpV1), has been characterized. However, the relationship between the abovementioned coccidian parasite and the virus has not been studied in the context of the known clinical outcomes. This study aimed to characterize the prevalence and molecular traits of CSpV1 in diarrheal feces of Hanwoo (Korean indigenous cattle) calves. Of the 140 fecal samples previously tested for C. parvum, which were obtained from Hanwoo calves aged 60 days, 70 tested positive and 70 tested negative. These samples were included in this study. By using the polymerase chain reaction (PCR) analysis targeting the RdRp gene of CSpV1, we detected CSpV1 in 28 samples (20.0%), with infection rates of 31.4% (22/70) in C. parvum-positive and 8.6% (6/70) in C. parvum-negative samples. CSpV1 samples detected in the same farm were clustered together. To the best of our knowledge, this is the first study to report the prevalence and molecular characteristics of CSpV1 in Hanwoo calves in the Republic of Korea, providing important insights into the relationship between C. parvum and CSpV1 in bovine hosts. [ABSTRACT FROM AUTHOR]

Published
2023
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