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Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control
Ko, Hyo Rim,Hwang, Inwoo,Jin, Eun-Ju,Yun, Taegwan,Ryu, Dongryeol,Kang, Jong-Sun,Park, Kye Won,Shin, Joo-Ho,Cho, Sung-Woo,Lee, Kyung-Hoon,Ye, Keqiang,Ahn, Jee-Yin National Academy of Sciences 2019 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.116 No.49
<P><B>Significance</B></P><P><I>Ebp1</I> deletion causes developmental defects with massive cell death and cessation of cell proliferation through dysregulation of epigenetic gene silencing unit, a Suv39H1/DNMT1 axis. Our study indicates that EBP1 regulates global gene expression via at least 2 mechnaisms. First, EBP1 acts as a transcriptional repressor for DNMT1 gene expression, allowing the escape of the repressive chromatin state. Second, EBP1 binds to the promoter region of the target gene inhibiting the association of DNMT1 with the downstream gene such as <I>Survivin</I>, regulating gene expression. Hence, these findings provide a molecular mechanism of how EBP1 functions in cell survival and transcriptional regulation by modulating epigenetic regulators during development.</P><P>ErbB3-binding protein 1 (EBP1) is implicated in diverse cellular functions, including apoptosis, cell proliferation, and differentiation. Here, by generating genetic inactivation of <I>Ebp1</I> mice, we identified the physiological roles of EBP1 in vivo. Loss of <I>Ebp1</I> in mice caused aberrant organogenesis, including brain malformation, and death between E13.5 and 15.5 owing to severe hemorrhages, with massive apoptosis and cessation of cell proliferation. Specific ablation of Ebp1 in neurons caused structural abnormalities of brain with neuron loss in [Nestin-Cre; <I>Ebp1</I><SUP><I>flox/flox</I></SUP>] mice. Notably, global methylation increased with high levels of the gene-silencing unit Suv39H1/DNMT1 in <I>Ebp1</I>-deficient mice. EBP1 repressed the transcription of <I>Dnmt1</I> by binding to its promoter region and interrupted DNMT1-mediated methylation at its target gene, <I>Survivin</I> promoter region. Reinstatement of EBP1 into embryo brain relived gene repression and rescued neuron death. Our findings uncover an essential role for EBP1 in embryonic development and implicate its function in transcriptional regulation.</P>
( Hyo Rim Ko ),( Inwoo Hwang ),( So Yoon Ahn ),( Yun Sil Chang ),( Won Soon Park ),( Jee-yin Ahn ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.3
P48 Ebp1 is expressed in rapidly proliferating cells such as cancer cells and accelerates cell growth and survival. However, its expression pattern and role in central nervous system development have not been studied. Here, we demonstrated the spatiotemporal expression pattern of p48 Ebp1 during embryonic development and the postnatal period. During embryonic development, p48 Ebp1 was highly expressed in the brain. Expression gradually decreased after birth but was still more abundant than p42 expression after birth. Strikingly, we found that p48 Ebp1 was expressed in a cell type specific manner in neurons but not astrocytes. Moreover, p48 Ebp1 physically interacted with beta tubulin but not alpha tubulin. This fits with its accumulation in distal microtubule growth cone regions. Furthermore, in injured hippocampal slices, p48 Ebp1 introduction promoted axon regeneration. Thus, we speculate that p48 Ebp1 might contribute to microtubule dynamics acting as an MAP and promotes CNS axon regeneration. [BMB Reports 2017; 50(3): 126-131]
P42 Ebp1 functions as a tumor suppressor in non-small cell lung cancer
( Hyo Rim Ko ),( Truong Lx Nguyen ),( Chung Kwon Kim ),( Young Bin Park ),( Kyung Hoon Lee ),( Jee Yin Ahn ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.3
Although the short isoform of ErbB3-binding protein 1 (Ebp1), p42 has been considered to be a potent tumor suppressor in a number of human cancers, whether p42 suppresses tumorigenesis of lung cancer cells has never been clarified. In the current study we investigated the tumor suppressor role of p42 in non-small cell lung cancer cells. Our data suggest that the expression level of p42 is inversely correlated with the cancerous properties of NSCLC cells and that ectopic expression of p42 is sufficient to inhibit cell proliferation, anchorage-independent growth, and invasion as well as tumor growth in vivo. Interestingly, p42 suppresses Akt activation and overexpression of a constitutively active form of Akt restores the tumorigenic activity of A549 cells that is ablated by exogenous p42 expression. Thus, we propose that p42 Ebp1 functions as a potent tumor suppressor of NSCLC through interruption of Akt signaling.[BMB Reports 2015; 48(3): 159-165]
Ko, Jeong Rim,Seo, Dae Yun,Park, Se Hwan,Kwak, Hyo Bum,Kim, Min,Ko, Kyung Soo,Rhee, Byoung Doo,Han, Jin Elsevier 2018 Biochemical and biophysical research communication Vol.501 No.2
<P><B>Abstract</B></P> <P>Cereblon (CRBN) has been reported as a negative regulator of adenosine monophosphate-activated protein kinase (AMPK). Aerobic exercise training has been shown to increase AMPK, which resulted in glucose regulation in skeletal muscle. However, the expression level of CRBN and its association with the physiological modulation of glucose are still unclear. Male Sprague-Dawley rats (5-week-old, n = 18) were assigned to control, streptozotocin (STZ, 65 mg/kg)-induced diabetic group, and STZ + exercise (STZ + EXE) group with six rats in each group. Rats in the STZ + EXE group exercised by treadmill running (20 m/min, 60 min, 4 times/week) for 8 weeks. Compared with the STZ group, blood glucose was significantly decreased in the STZ + EXE group. The skeletal muscle of rats in the STZ + EXE group showed a significant decrease in CRBN levels and an increase in AMPK, protein kinase B, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, fibronectin type III domain-containing protein 5, glucose transporter type 4, superoxide dismutase 1, and uncoupling protein 3 levels. These results suggest that CRBN is a potential regulator of glucose homeostasis in the skeletal muscle. Moreover, our results suggest that aerobic exercise training may provide an important physiological treatment for type 1 diabetes by decreasing CRBN and increasing AMPK signaling in skeletal muscle.</P> <P><B>Highlights</B></P> <P> <UL> <LI> STZ-induced diabetes increased levels of CRBN protein in the skeletal muscle. </LI> <LI> Aerobic exercise training attenuates level of CRBN protein and increases AMPK signaling in skeletal muscle. </LI> <LI> CRBN is a regulator of exercise-mediated anti-diabetic effect. </LI> </UL> </P>
Ko, Young-Joon,Lee, Hyang-Sim,Jeoung, Hye-Young,Heo, Eun-Jeong,Ko, Hyo-Rim,Chang, Byung-Sik,Joo, Hoo-Don,Gerelmaa, U.,Dashzeveg, B.,Tserendorj, S.,Sodnomdarjaa, R.,Park, Jong-Hyeon,Kweon, Chang-Hee,Ch American Society for Microbiology 2010 CLINICAL AND VACCINE IMMUNOLOGY Vol.17 No.1
<B>ABSTRACT</B><P>A blocking enzyme-linked immunosorbent assay (ELISA) with a baculovirus-expressed structural protein was developed for the detection of antibodies to foot-and-mouth disease virus type A. It exhibited 99% specificity with a cutoff of 53% inhibition. Its sensitivity was comparable to the sensitivities of the virus neutralization test and the liquid-phase blocking ELISA, indicating its potential as an alternative assay.</P>
B23/Nucleophosmin promotes reconstitution of synaptic path in hippocampus after injury
Yun, Taegwan,Ko, Hyo Rim,Ahn, Jaeyoung,Jin, Eun-Ju,Jo, Jung Min,Kwon, Il-Sun,Cho, Sung-Woo,Chang, Yun Sil,Park, Won Soon,Ahn, Jee-Yin Elsevier 2019 Biochemical and biophysical research communication Vol.508 No.4
<P><B>Abstract</B></P> <P>B23, also known as nucleophosmin (NPM), is multifunctional protein directly implicated in cell proliferation, cell cycle progression, and cell survival. In the current study, in addition to confirming its anti-apoptotic function in neuronal survival, we demonstrated that the spatial-temporal expression profile of B23 during development of hippocampal neurons is high in the embryonic stage, down-regulated after birth, and preferentially localized at the tips of growing neuritis and branching points. Overexpression of B23 promotes axon growth with abundant branching points in growing hippocampal neurons, but depletion of B23 impairs axon growth, leading to neuronal death. Following injury to the trisynaptic path in hippocampal slice, overexpression of B23 remarkably increased the number and length of regenerative fibers in the mossy fiber path. Our study suggests that B23 expression in developing neurons is essential for neuritogenesis and axon growth and that up-regulation of B23 may be a strategy for enhancing the reconstitution of synaptic paths after injury to hippocampal synapses.</P> <P><B>Highlights</B></P> <P> <UL> <LI> B23 is high in the embryonic stage and declined after birth in the developing brain. </LI> <LI> Overexpression of B23 enhances axon growth with abundant branching points. </LI> <LI> Depletion of B23 impairs axon growth, bring about neuronal death. </LI> <LI> B23 contributes to reinstate mossy fiber path in hippocampus after injury. </LI> </UL> </P>
Youngkwan Kim,Hyo Rim Ko,Inwoo Hwang,안지인 생화학분자생물학회 2024 BMB Reports Vol.57 No.4
Neural stem cells (NSCs) in the adult hippocampus divide infrequently;the endogenous molecules modulating adult hippocampalneurogenesis (AHN) remain largely unknown. Here,we show that ErbB3 binding protein 1 (Ebp1), which plays importantroles in embryonic neurodevelopment, acts as an essentialmodulator of adult neurogenic factors. In vivo analysisof Ebp1 neuron depletion mice showed impaired AHN with alow number of hippocampal NSCs and neuroblasts. Ebp1 leadsto transcriptional repression of Bmp4 and suppression of Ascl1promoter methylation in the dentate gyrus of the adult hippocampusreflecting an unusually high level of Bmp4 and lowAscl1 level in neurons of Ebp1-deficient mice. Therefore, ourfindings suggests that Ebp1 could act as an endogenous modulatorof the interplay between Bmp4 and Ascl1/Notch signaling,contributing to AHN.