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Won-Jae Lee drosophila

Jung Hoon Lee, Seoyoung Park, Yejin Yun, Won Hoon Choi, Min-Ji Kang, Min Jae Lee
BACKGROUND/AIMS: The 26S proteasome is the key proteolytic complex for recognition and degradation of polyubiquitinated target substrates in eukaryotes. Among numerous proteasome-associated proteins, a deubiquitinating enzyme (DUB) USP14 has been identified as an endogenous inhibitor of the proteasome. Here, we explored the complex regulatory functions of USP14 that involve ubiquitin (Ub) homeostasis and substrate degradation in flies and mammals. METHODS: USP14-null primary and immortalized mouse embryonic fibroblasts (MEFs) and USP14 knocked-down Drosophila were analyzed in this study...
May 9, 2018: Cellular Physiology and Biochemistry
Kyung-Ah Lee, Kyu-Chan Cho, Boram Kim, In-Hwan Jang, Kibum Nam, Young Eun Kwon, Myungjin Kim, Do Young Hyeon, Daehee Hwang, Jae-Hong Seol, Won-Jae Lee
DUOX, a member of the NADPH oxidase family, acts as the first line of defense against enteric pathogens by producing microbicidal reactive oxygen species. DUOX is activated upon enteric infection, but the mechanisms regulating DUOX activity remain incompletely understood. Using Drosophila genetic tools, we show that enteric infection results in "pro-catabolic" signaling that initiates metabolic reprogramming of enterocytes toward lipid catabolism, which ultimately governs DUOX homeostasis. Infection induces signaling cascades involving TRAF3 and kinases AMPK and WTS, which regulate TOR kinase to control the balance of lipogenesis versus lipolysis...
March 14, 2018: Cell Host & Microbe
Chang Geon Chung, Min Jee Kwon, Keun Hye Jeon, Do Young Hyeon, Myeong Hoon Han, Jeong Hyang Park, In Jun Cha, Jae Ho Cho, Kunhyung Kim, Sangchul Rho, Gyu Ree Kim, Hyobin Jeong, Jae Won Lee, TaeSoo Kim, Keetae Kim, Kwang Pyo Kim, Michael D Ehlers, Daehee Hwang, Sung Bae Lee
Dendrite aberration is a common feature of neurodegenerative diseases caused by protein toxicity, but the underlying mechanisms remain largely elusive. Here, we show that nuclear polyglutamine (polyQ) toxicity resulted in defective terminal dendrite elongation accompanied by a loss of Golgi outposts (GOPs) and a decreased supply of plasma membrane (PM) in Drosophila class IV dendritic arborization (da) (C4 da) neurons. mRNA sequencing revealed that genes downregulated by polyQ proteins included many secretory pathway-related genes, including COPII genes regulating GOP synthesis...
July 11, 2017: Cell Reports
Sandeep Kumar, In-Hwan Jang, Chan Woo Kim, Dong-Won Kang, Won Jae Lee, Hanjoong Jo
Disturbed blood flow (d-flow) induces atherosclerosis by altering the expression of mechanosensitive genes in the arterial endothelium. Previously, we identified >580 mechanosensitive genes in the mouse arterial endothelium, but their role in endothelial inflammation is incompletely understood. From this set, we obtained 84 Drosophila RNAi lines that silences the target gene under the control of upstream activation sequence (UAS) promoter. These lines were crossed with C564-GAL4 flies expressing GFP under the control of drosomycin promoter, an NF-κB target gene and a marker of pathogen-induced inflammation...
November 7, 2016: Scientific Reports
Kyung-Ah Lee, Boram Kim, Hyejin You, Won-Jae Lee
Intestinal dual oxidase (DUOX) activation is the first line of host defense against enteric infection in Drosophila. DUOX enzymatic activity is mainly controlled by phospholipase C-β (PLCβ)-dependent calcium mobilization, whereas DUOX gene expression is mainly controlled by the MEKK1-p38 mitogen-activated protein kinase pathway. Furthermore, bacterial-derived uracil molecules act as ligands for DUOX activation. However, our current understanding of uracil-induced signal transduction pathways remain incomplete...
2015: Fly
Do-Young Park, Won Jun Lee, In-Hwan Jang, Won-Jae Lee
Although Lactobacilli are generally considered probiotic agents in metazoans, the underlying molecular mechanisms are largely unknown. In this issue of Cell Host & Microbe, Erkosar et al. (2015) reveal that a Drosophila gut commensal, Lactobacillus plantarum(WJL), promotes animal growth by enhancing the host's capacity for protein degradation.
October 14, 2015: Cell Host & Microbe
Sujin Park, Yangsin Lee, Jin Won Pak, Hanbyeol Kim, Hyeonjin Choi, Jae-woo Kim, Jürgen Roth, Jin Won Cho
O-GlcNAcylation is a dynamic post-translational modification that takes place on ser/thr residues of nucleocytoplasmic proteins. O-GlcNAcylation regulates almost all cellular events as a nutrient sensor, a transcriptional and translational regulator, and a disease-related factor. Although the role of O-GlcNAcylation in insulin signaling and metabolism are well established, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we manipulated O-GlcNAcylation in Drosophila and found that it regulates autophagy through Akt/dFOXO signaling...
August 2015: Cellular and Molecular Life Sciences: CMLS
Sung Jun Bae, Myungjin Kim, Sung-Hee Kim, Young Eun Kwon, Ji-Hoon Lee, Jaesang Kim, Chin Ha Chung, Won-Jae Lee, Jae Hong Seol
The Hippo pathway plays crucial roles in regulating organ size and stem cell homeostasis. Although the signalling cascade of the core Hippo kinases is relatively well understood, little is known about the mechanisms that modulate the activity of the Hippo pathway. Here, we report identification of NEDD4, a HECT-type E3 ubiquitin ligase, as a regulatory component of the Hippo pathway. We demonstrate that NEDD4 ubiquitylates and destabilizes WW45 and LATS kinase, both of which are required for active Hippo signalling...
February 18, 2015: Nature Communications
Kyung-Ah Lee, Boram Kim, Jinhyuk Bhin, Do Hun Kim, Hyejin You, Eun-Kyoung Kim, Sung-Hee Kim, Ji-Hwan Ryu, Daehee Hwang, Won-Jae Lee
Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes...
February 11, 2015: Cell Host & Microbe
Hyejin You, Won Jun Lee, Won-Jae Lee
The metabolic activities of a given gut bacterium or gut commensal community fluctuate in a manner largely depending on the physicochemical parameters within the gut niche. Recognition of the bacterial metabolic status in situ, by a sensing of the gut metabolites as a signature of a specific bacterial metabolic activity, has been suggested to be a highly beneficial means for the host to maintain gut-microbe homeostasis. Recently, analysis of Drosophila gut immunity revealed that bacterial-derived uracil and uracil-modulated intestinal reactive oxygen species (ROS) generation play a pivotal role in diverse aspects of host-microbe interactions, such as pathogen clearance, commensal protection, intestinal cell regeneration, colitogenesis, and possibly also interorgan immunological communication...
October 2014: Current Opinion in Immunology
Won-Jae Lee, Masayuki Miura
In response to cellular and tissue losses caused by physical or chemical injuries, organisms must activate multiple wound repair systems at the cellular, tissue, and organismal levels. The systemic wound response (SWR) that occurs via interorgan communication between local wound sites and remote organs ensures that the host is protected efficiently in response to a local wound. The local wound response around the wound site is fairly well documented, but the molecular mechanisms that allow the host to launch SWR are poorly understood...
2014: Current Topics in Developmental Biology
Sung-Hee Kim, Won-Jae Lee
It is well-known that certain bacterial species can colonize the gut epithelium and induce inflammation in the mucosa, whereas other species are either benign or beneficial to the host. Deregulation of the gut-microbe interactions may lead to a pathogenic condition in the host, such as chronic inflammation, tissue injuries, and even cancer. However, our current understanding of the molecular mechanisms that underlie gut-microbe homeostasis and pathogenesis remains limited. Recent studies have used Drosophila as a genetic model to provide novel insights into the causes and consequences of bacterial-induced colitis in the intestinal mucosa...
2014: Frontiers in Cellular and Infection Microbiology
Eun-Kyoung Kim, Young Min Park, Oun Young Lee, Won-Jae Lee
Lactobacillus brevis strain EW, a gut pathobiont, was isolated from the fruit fly Drosophila melanogaster. Here, we report the draft genome sequence of L. brevis EW.
2013: Genome Announcements
Eun-Kyoung Kim, Young Min Park, Oun Young Lee, Won-Jae Lee
Lactobacillus plantarum strain WJL, a member of the symbiotic gut bacteria, was isolated from the intestine of the fruit fly, Drosophila melanogaster. Here, we report the draft genome sequence of L. plantarum WJL.
2013: Genome Announcements
Won-Jae Lee, Paul T Brey
Since Metchnikoff developed his views on the intestinal microflora, much effort has been devoted to understanding the role of gut microbiomes in metazoan physiology. Despite impressive data sets that have been generated by associating a phenotype-causing commensal community with its corresponding host phenotype, the field continues to suffer from descriptive and often contradictory reports. Hence, we cannot yet draw clear conclusions as to how the modifications of microbiomes cause physiological changes in metazoans...
2013: Annual Review of Cell and Developmental Biology
Qingling Xu, Kyung-Ah Lee, Songyi Lee, Kyung Mi Lee, Won-Jae Lee, Juyoung Yoon
Oxidative stress induced by reactive oxygen species (ROS) plays crucial roles in a wide range of physiological processes and is also implicated in various diseases, including cancer, chronic inflammatory diseases, and neurodegenerative disorders. Among the various ROS, hypochlorous acid (HOCl) plays as a powerful microbicidal agent in the innate immune system. The regulated production of microbicidal HOCl is required for the host to control the invading microbes. However, as a result of the highly reactive and diffusible nature of HOCl, its uncontrolled production may lead to an adverse effect on host physiology...
July 3, 2013: Journal of the American Chemical Society
Kyung-Ah Lee, Won-Jae Lee
The association between deregulated intestinal microbial consortia and host diseases has been recognized since the birth of microbiology over a century ago. Intestinal dysbiosis refers to a state where living metazoans harbor harmful intestinal microflora. However, there is still an issue of whether causality arises from the host or the microbe because it is unclear whether deregulation of the gut microbiota community is the consequence or cause of the host disease. Recent studies using Drosophila and its simple microbiota have provided a valuable model system for dissecting the molecular mechanisms of intestinal dysbiosis...
January 2014: Developmental and Comparative Immunology
Kyung-Ah Lee, Sung-Hee Kim, Eun-Kyoung Kim, Eun-Mi Ha, Hyejin You, Boram Kim, Min-Ji Kim, Youngjoo Kwon, Ji-Hwan Ryu, Won-Jae Lee
All metazoan guts are subjected to immunologically unique conditions in which an efficient antimicrobial system operates to eliminate pathogens while tolerating symbiotic commensal microbiota. However, the molecular mechanisms controlling this process are only partially understood. Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species...
May 9, 2013: Cell
Sang Mi Shim, Won Jae Lee, Youngdoo Kim, Jong Wook Chang, Sungmin Song, Yong-Keun Jung
The ubiquitin-proteasome system is essential for maintaining protein homeostasis. However, proteasome dysregulation in chronic diseases is poorly understood. Through genome-wide cell-based screening using 5,500 cDNAs, a signaling pathway leading to NFκB activation was selected as an inhibitor of 26S proteasome. TNF-α increased S5b (HGNC symbol PSMD5; hereafter S5b/PSMD5) expression via NFκB, and the surplus S5b/PSMD5 directly inhibited 26S proteasome assembly and activity. Downregulation of S5b/PSMD5 abolished TNF-α-induced proteasome inhibition...
September 27, 2012: Cell Reports
Jwa-Jin Kim, Hye-Mi Lee, Dong-Min Shin, Wonho Kim, Jae-Min Yuk, Hyo Sun Jin, Sang-Hee Lee, Guang-Ho Cha, Jin-Man Kim, Zee-Won Lee, Sung Jae Shin, Heekyung Yoo, Young Kil Park, Jin Bong Park, Jongkyeong Chung, Tamotsu Yoshimori, Eun-Kyeong Jo
The current standard of treatment against tuberculosis consists of a cocktail of first-line drugs, including isoniazid and pyrazinamide. Although these drugs are known to be bactericidal, contribution of host cell responses in the context of antimycobacterial chemotherapy, if any, remains unknown. We demonstrate that isoniazid and pyrazinamide promote autophagy activation and phagosomal maturation in Mycobacterium tuberculosis (Mtb)-infected host cells. Treatment of Mtb-infected macrophages with isoniazid or pyrazinamide caused significant activation of cellular and mitochondrial reactive oxygen species and autophagy, which was triggered by bacterial hydroxyl radical generation...
May 17, 2012: Cell Host & Microbe
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