Hong Jo Lee, Hyung Chul Lee, and Jae Yong HanMol. Cells 2015; 38(9): 743-749 https://doi.org/10.14348/molcells.2015.0225
Abstract : Production of genome-edited animals using germline-competent cells and genetic modification tools has provided opportunities for investigation of biological mechanisms in various organisms. The recently reported programmed genome editing technology that can induce gene modification at a target locus in an efficient and precise manner facilitates establishment of animal models. In this regard, the demand for genome-edited avian species, which are some of the most suitable model animals due to their unique embryonic development, has also increased. Furthermore, germline chimera production through long-term culture of chicken primordial germ cells (PGCs) has facilitated research on production of genome-edited chickens. Thus, use of avian germline modification is promising for development of novel avian models for research of disease control and various biological mechanisms. Here, we discuss recent progress in genome modification technology in avian species and its applications and future strategies.
Seung Min Jeong, and Marcia C. HaigisMol. Cells 2015; 38(9): 750-758 https://doi.org/10.14348/molcells.2015.0167
Abstract : Genomic instability and altered metabolism are key features of most cancers. Recent studies suggest that metabolic reprogramming is part of a systematic response to cellular DNA damage. Thus, defining the molecules that fine-tune metabolism in response to DNA damage will enhance our understanding of molecular mechanisms of tumorigenesis and have profound implications for the development of strategies for cancer therapy. Sirtuins have been established as critical regulators in cellular homeostasis and physiology. Here, we review the emerging data revealing a pivotal function of sirtuins in genome maintenance and cell metabolism, and highlight current advances about the phenotypic consequences of defects in these critical regulators in tumorigenesis. While many questions should be addressed about the regulation and context-dependent functions of sirtuins, it appears clear that sirtuins may provide a promising, exciting new avenue for cancer therapy.
Na-Rae Lee, Hye-In Kim, Myung-Soo Choi, Chae-Min Yi, and Kyung-Soo InnMol. Cells 2015; 38(9): 759-764 https://doi.org/10.14348/molcells.2015.0047
Abstract : Tripartite motif protein 25 (TRIM25), mediates K63-linked polyubiquitination of Retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. Here, we demonstrate that TRIM25 is required for melanoma differentiation-associated gene 5 (MDA5) and MAVS mediated activation of NF-κB and interferon production. TRIM25 is required for the full activation of NF-κB at the downstream of MAVS, while it is not involved in IRF3 nuclear translocation. Mechanical studies showed that TRIM25 is involved in TRAF6-mediated NF-κB activation. These collectively indicate that TRIM25 plays an additional role in RIG-I/MDA5 signaling other than RIG-I ubiquitination via activation of NF-κB.
Hye-Sun Lim, Hyekyung Ha, Hyeun-Kyoo Shin, and Soo-Jin JeongMol. Cells 2015; 38(9): 765-772 https://doi.org/10.14348/molcells.2015.0062
Gunsup Lee, SeungChan Cho, Phuong Mai Hoang, Dongjun Kim, Yongjun Lee, Eui-Joon Kil, Sung-June Byun, Taek-Kyun Lee, Dae-Hyun Kim, Sunghan Kim, and Sukchan LeeMol. Cells 2015; 38(9): 773-780 https://doi.org/10.14348/molcells.2015.0073
Abstract : 3D8 single chain variable fragment (scFv) is a recombinant monoclonal antibody with nuclease activity that was originally isolated from autoimmune-prone MRL mice. In a previous study, we analyzed the nuclease activity of 3D8 scFv and determined that a HeLa cell line expressing 3D8 scFv conferred resistance to herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV). In this study, we demonstrate that 3D8 scFv could be delivered to target tissues and cells where it exerted a therapeutic effect against PRV. PRV was inoculated via intramuscular injection, and 3D8 scFv was injected intraperitoneally. The observed therapeutic effect of 3D8 scFv against PRV was also supported by results from quantitative reverse transcription polymerase chain reaction, southern hybridization, and immunohistochemical assays. Intraperitoneal injection of 5 and 10 μg 3D8 scFv resulted in no detectable toxicity. The survival rate in C57BL/6 mice was 9% after intramuscular injection of 10 LD50 PRV. In contrast, the 3D8 scFv-injected C57BL/6 mice showed survival rates of 57% (5 μg) and 47% (10 μg). The results indicate that 3D8 scFv could be utilized as an effective antiviral agent in several animal models.
Mun Young Chang, Ah Reum Kim, Nayoung K.D. Kim, Chung Lee, Kyoung Yeul Lee, Woo-Sung Jeon, Ja-Won Koo, Seung Ha Oh, Woong-Yang Park, Dongsup Kim, and Byung Yoon ChoiMol. Cells 2015; 38(9): 781-788 https://doi.org/10.14348/molcells.2015.0078
Abstract : Mutations of
Kiwon Lee, Ji Hye Kim, and Hyockman KwonMol. Cells 2015; 38(9): 789-795 https://doi.org/10.14348/molcells.2015.0109
Abstract : A chromosome territory is composed of chromosomal subdomains. The internal structure of chromosomal subdomains provides a structural framework for many genomic activities such as replication and DNA repair, and thus is key to determining the basis of their mechanisms. However, the internal structure and regulating proteins of a chromosomal subdomain remains elusive. Previously, we showed that the chromosome territory expanded after BAF53 knockdown. Because the integrity of chromosomal subdomains is a deciding factor of the volume of a chromosome territory, we examined here the effect of BAF53 knockdown on chromosomal subdomains. We found that BAF53 knockdown led to the disintegration of histone H2B-GFP-visualized chromosomal subdomains and BrdU-labeled replication foci. In addition, the size of DNA loops measured by the maximum fluorescent halo technique increased and became irregular after BAF53 knockdown, indicating DNA loops were released from the residual nuclear structure. These data can be accounted for by the model that BAF53 is prerequisite for maintaining the structural integrity of chromosomal subdomains.
Hyeon-Joong Kim, Eun-Joo Shin, Byung-Hwan Lee, Sun-Hye Choi, Seok-Won Jung, Ik-Hyun Cho, Sung-Hee Hwang, Joon Yong Kim, Jung-Soo Han, ChiHye Chung, Choon-Gon Jang, Hyewon Rhim, Hyoung-Chun Kim, and Seung-Yeol NahMol. Cells 2015; 38(9): 796-805 https://doi.org/10.14348/molcells.2015.0116
Abstract : Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer’s disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system
Hyun Lee, Jae-sung Bae, and Hee Kyung JinMol. Cells 2015; 38(9): 806-813 https://doi.org/10.14348/molcells.2015.0117
Abstract : Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the glucocerebrosidase gene (
Ponnarath Keo, Joong Sub Choi, Jaeman Bae, Yhong-Hee Shim, and Bong-Kyeong OhMol. Cells 2015; 38(9): 814-820 https://doi.org/10.14348/molcells.2015.0144
Abstract : PinX1, a nucleolar protein of 328 amino acids, inhibits telomerase activity, which leads to the shortening of telomeres. The C-terminal region of PinX1 is responsible for its nucleolar localization and binding with TERT, a catalytic component of telomerase. A fraction of TERT localizes to the nucleolus, but the role of TERT in the nucleolus is largely unknown. Here, we report a functional connection between PinX1 and TERT regarding PinX1 stability. The C-terminal of PinX1205?328, a nucleolar fragment, was much more stable than the N-terminal of PinX11?204, a nuclear fragment. Interestingly, PinX1 was less stable in TERT-depleted cells and more stable in TERT-myc expressing cells. Stability assays for PinX1 truncation forms showed that both PinX11?328 and PinX1205?328, nucleolar forms, were more rapidly degraded in TERT-depleted cells, while they were more stably maintained in TERT-overexpressing cells, compared to each of the controls. However, PinX11?204 was degraded regardless of the TERT status. These results reveal that the stability of PinX1 is maintained in nucleolus in the presence of TERT and suggest a role of TERT in the regulation of PinX1 steady-state levels.