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ANKRD9 is associated with tumor suppression as a substrate receptor subunit of ubiquitin ligase
Lee, Yejin,Lim, Byungho,Lee, Seon Woo,Lee, Woo Rin,Kim, Yong-In,Kim, Minhyeok,Ju, Hyoungseok,Kim, Mi Young,Kang, Suk-Jo,Song, Ji-Joon,Lee, J. Eugene,Kang, Changwon Elsevier 2018 Biochimica et biophysica acta. Molecular basis of Vol.1864 No.10
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Human <I>ANKRD9</I> (ankyrin repeat domain 9) expression is altered in some cancers.</P> <P><B>Methods</B></P> <P>We tested genetic association of ANKRD9 with gastric cancer susceptibility and examined functional association of ANKRD9 with altered proliferation of MKN45 gastric cancer cells. We then identified ANKRD9-binding partners in HEK 293 embryonic kidney cells using quantitative proteomics, western blotting and complex reconstitution assays. We finally demonstrated ANKRD9's role of recognizing substrates for ubiquitination using in vitro ubiquitylation assay.</P> <P><B>Results</B></P> <P> <I>ANKRD9</I> is associated with cancer susceptibility in a comparison of single-nucleotide polymorphisms between 1092 gastric cancer patients and 1206 healthy controls. ANKRD9 depletion accelerates tumor progression by increasing cellular proliferation, piling up, and anchorage-independent growth of MKN45 cells. We discovered that ANKRD9 is a ubiquitin ligase substrate receptor subunit and has an anti-proliferative activity. ANKRD9 associates with CUL5 (not CUL2), ELOB, ELOC, and presumably RNF7 subunits, which together assemble into a cullin-RING superfamily E3 ligase complex. ANKRD9 belongs to the ASB family of proteins, which are characterized by the presence of ankyrin repeats and a SOCS box. In addition to its interactions with the other E3 ligase subunits, ANKRD9 interacts with two isoforms of inosine monophosphate dehydrogenase (IMPDH). These IMPDH isoforms are cognate substrates of the ANKRD9-containing E3 enzyme, which ubiquitinates them for proteasomal degradation. Their ubiquitination and turnover require the presence of ANKRD9.</P> <P><B>Conclusion</B></P> <P>ANKRD9, a previously unidentified E3 substrate receptor subunit, functions in tumor suppression by recognizing the oncoprotein IMPDH isoforms for E3 ubiquitination and proteasomal degradation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Human <I>ANKRD9</I> is genetically associated with gastric cancer susceptibility. </LI> <LI> ANKRD9 protein activity is functionally associated with tumor suppression. </LI> <LI> ANKRD9 is a substrate receptor subunit of CUL5-based ubiquitin ligase E3 complex. </LI> <LI> E3 with ANKRD9 ubiquitinates substrate proteins for proteasomal degradation. </LI> <LI> Two isoforms of oncoprotein IMP dehydrogenase are cognate substrates of ANKRD9. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Minhyeok Lee,Ji Hye Kim,정인범,Ji Woong Son,Moon Jun Na,권선중 대한중환자의학회 2019 Acute and Critical Care Vol.34 No.1
Background:Use of a high-flow nasal cannula (HFNC) reduced postextubation respiratory failure (PERF) and reintubation rate compared to use of a low-flow oxygen system (LFOS) in low-risk patients. However, no obvious conclusion was reached for high-risk patients. Here, we sought to present the current status of HFNC use as adjunctive oxygen therapy in a clinical setting and to elucidate the nature of the protective effect following extubation. Methods:The medical records of 855 patients who were admitted to the intensive care unit of single university hospital during a period of 5.5 years were analyzed retrospectively, with only 118 patients ultimately included in the present research. The baseline characteristics of these patients and the occurrence of PERF and reintubation along with physiologic changes were analyzed. Results:Eighty-four patients underwent HFNC, and the remaining 34 patients underwent conventional LFOS after extubation. Physicians preferred HFNC to LFOS in the face of highrisk features including old age, neurologic disease, moderate to severe chronic obstructive pulmonary disease, a long duration of mechanical ventilation, low baseline arterial partial pressure of oxygen to fraction of inspired oxygen ratio, and a high baseline alveolar–arterial oxygen difference. The reintubation rate at 72 hours after extubation was not different (9.5% vs. 8.8%; P=1.000). Hypoxic respiratory failure was slightly higher in the nonreintubation group than in the reintubation group (31.9% vs. 6.7%; P=0.058). Regarding physiologic effects, heart rate was only stabilized after 24 hours of extubation in the HFNC group. Conclusions:No difference was found in the occurrence of PERF and reintubation between both groups. It is worth noting that similar PERF and reintubation ratios were shown in the HFNC group in those with certain exacerbating risk factors versus not. Caution is needed regarding delayed reintubation in the HFNC group.
HELLP syndrome in a pregnant patient with Gitelman syndrome
( Minhyeok Lee ),( Dong-il Kim ),( Kyung-ho Lee ),( Jun-hyun Byun ),( Jiyong Hwang ),( Won-min Hwang ),( Sung-ro Yun ),( Se-hee Yoon ) 대한신장학회 2017 Kidney Research and Clinical Practice Vol.36 No.1
Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks` gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.
Lee Yeji,Park Jeanho,Kim Yerin,Hwang Hyunjoo,Jin Caiquan,Oh Yoojin,Kang Yangjoo,Lee Daehwan,Song Minhyeok,Lee Yoonji,고기성,Hong Mineui 한국원예학회 2024 원예과학기술지 Vol.42 No.3
The rabies virus causes neurological infections, resulting in the deaths of over 60,000 people worldwide each year. Currently available rabies vaccines are attenuated virus vaccines, which carry the risk of transmission among both humans and animals. An exciting alternative to these traditional vaccines is the use of recombinant plant-based vaccines. In this study, we applied the rabies virus glycoprotein (RVGP) as a recombinant vaccine to be transiently expressed in plants. To achieve this, we fused human immunoglobulin G Fc with the KDEL sequence, a motif for endoplasmic reticulum (ER) retention (FcK), to the RVGP, to generate RVGP-FcK. We then cloned the RVGPFcK gene expression cassette into the pEAQ vector and agro-infiltrated Agrobacterium tumefaciens (LBA4404) carrying the pEAQ RVGP-FcK vector into the leaves of Nicotiana benthamiana for transient expression. A RT-PCR analysis confirmed the transcription of the RVGP-FcK gene, which was evident as early as four days post-infiltration (dpi). To optimize the spatial and temporal aspects of RVGP-FcK production, we conducted analyses of its expression levels at different leaf positions (top, middle, and base) and dpi. A western blot analysis demonstrated that the RVGP-FcK protein reached its highest expression level at 7 dpi in the top leaf position and at 5 dpi in the middle leaf position. However, no detectable expression was observed in the bottom leaves at any time point. Subsequently, we validated the functionality of RVGP-FcK through an ELISA analysis. The results revealed that RVGP-FcK was expressed and assembled into its functional form most effectively at 5 and 7 dpi in the top leaf position and at 5 and 7 dpi in the middle leaf position. Our findings demonstrate that the transient expression of a functional RVGP-FcK protein can be optimized spatially and temporally in plants.
Enhanced Charge Injection in Pentacene Field‐Effect Transistors with Graphene Electrodes
Lee, Sangchul,Jo, Gunho,Kang, Seok‐,Ju,Wang, Gunuk,Choe, Minhyeok,Park, Woojin,Kim, Dong‐,Yu,Kahng, Yung Ho,Lee, Takhee Wiley - VCH Verlag GmbH & Co. KGaA 2011 Advanced Materials Vol. No.
<P><B>Pentacene organic field‐effect transistors</B> with multilayer graphene electrodes exhibit a lower contact resistance and lower charge‐injection barrier height than those with conventional Au electrodes. This enhancement in performance is related to the favorable dipole layer formation at the graphene/pentacene interface. </P>
A Comparison of Two-Stage Approaches Based on Penalized Regression for Estimating Gene Networks
Lee, Minhyeok,Seok, Junhee,Tae, Donghyun,Zhong, Hua,Han, Sung Won Mary Ann Liebert 2017 Journal of computational biology Vol.24 No.7
<P>Graphical models are commonly used for illustrating gene networks. However, estimating directed networks are generally challenging because of the limited sample size compared with the dimensionality of an experiment. Many previous studies have provided insight into the problem, and recently, two-stage approaches have shown significant improvements for estimating directed acyclic graphs. These two-stage approaches find neighborhoods in the first stage and determine the directions of the edges in the second stage. However, although numerous methods to find neighborhoods and determine directions exist, the most appropriate method to use with two-stage approaches has not been evaluated. Therefore, we compared such methods through extensive simulations to select effective methods for the first and second stages. Results show that adaptive lasso is the most effective for both stages in most cases. In addition, we compared methods to handle asymmetric entries to estimate an undirected network. Some previous studies indicate that the method used to handle asymmetric entries does not affect performance significantly; however, we found that the selection of the handling method for such edges is a significant factor for finding neighborhoods when using adaptive lasso.</P>