• Title/Summary/Keyword: Post-regulator

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Protein Interaction Mapping of Translational Regulators Affecting Expression of the Critical Stem Cell Factor Nos

  • Malik, Sumira;Jang, Wijeong;Kim, Changsoo
    • Development and Reproduction
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    • v.21 no.4
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    • pp.449-456
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    • 2017
  • The germline stem cells of the Drosophila ovary continuously produce eggs throughout the life-span. Intricate regulation of stemness and differentiation is critical to this continuous production. The translational regulator Nos is an intrinsic factor that is required for maintenance of stemness in germline stem cells. Nos expression is reduced in differentiating cells at the post-transcriptional level by diverse translational regulators. However, molecular mechanisms underlying Nos repression are not completely understood. Through three distinct protein-protein interaction experiments, we identified specific molecular interactions between translational regulators involved in Nos repression. Our findings suggest a model in which protein complexes assemble on the 3' untranslated region of Nos mRNA in order to regulate Nos expression at the post-transcriptional level.

Post-transcriptional Regulation of Gcn5, a Putative Regulator of Hox in Mouse Embryonic Fibroblast Cells

  • Lee, You-Ra;Oh, Ji-Hoon;Kong, Kyoung-Ah;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.165-168
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    • 2012
  • Hox proteins containing DNA-binding homedomain act as transcription factors important for anteroposterior body patterning during vertebrate embryogenesis. However, the precise mechanisms by which signal pathways are transduced to regulate the Hox gene expression are not clear. In the course of an attempt to isolate an upstream regulatory factor(s) controlling Hox genes, protein kinase B alpha (Akt1) has been identified as a putative regulator of Hox genes through in silico analysis (GEO profile). In the Gene Expression Omnibus (GEO) dataset GDS1784 at the NCBI (National Center for Biotechnology Information) site, Hox genes were differentially expressed depending on the presence or absence of Akt1. Since it was not well known how Akt1 regulates the specific Hox genes, whose transcription was reported to be regulated by epigenetic modifications such as histone acetylation, methylation etc., the expression of Gcn5, a histone acetyltransferase (HAT), was analyzed in wild type (WT) as well as in $Akt1^{-/-}$ mouse embryonic fibroblast (MEF) cells. RT-PCR analysis revealed that the amount of Gcn5 mRNA was similar in both WT and $Akt1^{-/-}$ MEFs. However, the protein level of Gcn5 was significantly increased in $Akt1^{-/-}$ MEF cells. The half life of Gcn5 was 1 hour in wild type whereas 8 hours in $Akt1^{-/-}$ MEF. These data all together, indicate that Gcn5 is post-transcriptionally down-regulated and the protein stability is negatively regulated by Akt1 in MEF cells.

A Design of Ultra-low Noise LDO Regulator for Low Voltage MEMS Microphones (저전압 MEMS 마이크로폰용 초저잡음 LDO 레귤레이터 설계)

  • Moon, Jong-il;Nam, Chul;Yoo, Sang-sun
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2021.10a
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    • pp.630-633
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    • 2021
  • Microphones can convert received voice signals to electric signals. They have been widely used in various industries such as radios, smart devices and vehicles. Recently, the demands for small size and high sensitive microphones are increased according to the minimization of wireless earphone with the development of smart phone. A MEMS system is a good candidate for an ultra-small size microphone of a next generation and a read out IC for high sensitive MEMS sensor is researched from many industries and academies. Since the microphone system has a high sensitivity from environment noise and electric system noise, the system requires a low noise power supply and some low noise design techniques. In this paper, a low noise LDO is presented for small size MEMS microphone systems. The input supply voltage of the LDO is 1.5-3.6V, and the output voltage is 1.3V. Then, it can support to 5mA in the light load condition. The integrated output noise of proposed LDO form 20Hz to 20kHz is about 1.9uV. These post layout simulation results are performed with TSMC 0.18um CMOS technology and the size of layout is 325㎛ × 165㎛.

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Alternative splicing and expression analysis of High expression of osmotically responsive genes1 (HOS1) in Arabidopsis

  • Lee, Jeong-Hwan;Kim, Soo-Hyun;Kim, Jae-Joon;Ahn, Ji-Hoon
    • BMB Reports
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    • v.45 no.9
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    • pp.515-520
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    • 2012
  • High expression of osmotically responsive genes1 (HOS1), a key regulator of low temperature response and flowering time, encodes an E3 ubiquitin ligase in Arabidopsis. Here, we report characterization of a newly identified splice variant (HOS1-L) of HOS1. Comparative analyses revealed that HOS1-L has a longer 5' nucleotide sequence than that of the previously identified HOS1 (HOS1-S) and that its protein sequence was more conserved than that of HOS1-S in plants. HOS1-L transcripts were spatio-temporally more abundant than those of HOS1-S. The recovery rate of HOS1-S expression was faster than that of HOS1-L after cold treatment. Diurnal oscillation patterns of HOS1-L revealed that HOS1-L expression was affected by photoperiod. An in vitro pull-down assay revealed that the HOS1-L protein interacted with the ICE1 protein. HOS1-L overexpression caused delayed flowering in wild-type plants. Collectively, these results suggest regulation of HOS1 expression at the post-transcriptional level.

Down-regulation of the cyclin E1 oncogene expression by microRNA-16-1 induces cell cycle arrest in human cancer cells

  • Wang, Fu;Fu, Xiang-Dong;Zhou, Yu;Zhang, Yi
    • BMB Reports
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    • v.42 no.11
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    • pp.725-730
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    • 2009
  • Cyclin E1 (CCNE1), a positive regulator of the cell cycle, controls the transition of cells from G1 to S phase. In numerous human tumors, however, CCNE1 expression is frequently dysregulated, while the mechanism leading to its dysregulation remains incompletely defined. Herein, we showed that CCNE1 expression was subject to post-transcriptional regulation by a microRNA miR-16-1. This was evident at protein level of CCNE1 as well as its mRNA level. Further evident by dual luciferase reporter assay revealed that two evolutionary conserved binding sites on 3' UTR of CCNE1 were the direct functional target sites. Moreover, we showed that miR-16-1 induced G0/G1 cell cycle arrest by targeting CCNE1 and siRNA against CCNE1 partially phenocopied miR-16-1-induced cell cycle phenotype whereas substantially rescued anti-miR-16-1- induced phenotype. Together, all these results demonstrate that miR-16-1 plays a vital role in modulating cellular process in human cancers and indicate the therapeutic potential of miR-16-1 in cancer therapy.

Revisiting PPARγ as a target for the treatment of metabolic disorders

  • Choi, Sun-Sil;Park, Jiyoung;Choi, Jang Hyun
    • BMB Reports
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    • v.47 no.11
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    • pp.599-608
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    • 2014
  • As the prevalence of obesity has increased explosively over the last several decades, associated metabolic disorders, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases, have been also increased. Thus, new strategies for preventing and treating them are needed. The nuclear peroxisome proliferator-activated receptors (PPARs) are involved fundamentally in regulating energy homeostasis; thus, they have been considered attractive drug targets for addressing metabolic disorders. Among the PPARs, $PPAR{\gamma}$ is a master regulator of gene expression for metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of the thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects, such as weight gain, fluid retention, and cardiovascular dysfunction. Recently, many reports have suggested that $PPAR{\gamma}$ could be modulated by post-translational modifications (PTMs), and modulation of PTM has been considered as novel approaches for treating metabolic disorders with fewer side effects than the TZDs. In this review, we discuss how PTM of $PPAR{\gamma}$ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of $PPAR{\gamma}$.

A chaperone surveillance system in plant circadian rhythms

  • Cha, Joon-Yung;Khaleda, Laila;Park, Hee Jin;Kim, Woe-Yeon
    • BMB Reports
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    • v.50 no.5
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    • pp.235-236
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    • 2017
  • The circadian clock is an internal system that is synchronized by external stimuli, such as light and temperature, and influences various physiological and developmental processes in living organisms. In the model plant Arabidopsis, transcriptional, translational and post-translational processes are interlocked by feedback loops among morning- and evening-phased genes. In a post-translational loop, plant-specific single-gene encoded GIGANTEA (GI) stabilize the F-box protein ZEITLUPE (ZTL), driving the targeted-proteasomal degradation of TIMING OF CAB EXPRESSION 1 (TOC1) and PSEUDO-RESPONSE REGULATOR 5 (PRR5). Inherent to this, we demonstrate the novel biochemical function of GI as a chaperone and/or co-chaperone of Heat-Shock Protein 90 (HSP90). GI prevents ZTL degradation as a chaperone and facilitates ZTL maturation together with HSP90/HSP70, enhancing ZTL activity in vitro and in planta. GI is known to be involved in a wide range of physiology and development as well as abiotic stress responses in plants, but it could also interact with diverse client proteins to increase protein maturation. Our results provide evidence that GI helps proteostasis of ZTL by acting as a chaperone and a co-chaperone of HSP90 for proper functioning of the Arabidopsis circadian clock.

RNA Binding Protein-Mediated Post-Transcriptional Gene Regulation in Medulloblastoma

  • Bish, Rebecca;Vogel, Christine
    • Molecules and Cells
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    • v.37 no.5
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    • pp.357-364
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    • 2014
  • Medulloblastoma, the most common malignant brain tumor in children, is a disease whose mechanisms are now beginning to be uncovered by high-throughput studies of somatic mutations, mRNA expression patterns, and epigenetic profiles of patient tumors. One emerging theme from studies that sequenced the tumor genomes of large cohorts of medulloblastoma patients is frequent mutation of RNA binding proteins. Proteins which bind multiple RNA targets can act as master regulators of gene expression at the post-transcriptional level to co-ordinate cellular processes and alter the phenotype of the cell. Identification of the target genes of RNA binding proteins may highlight essential pathways of medulloblastomagenesis that cannot be detected by study of transcriptomics alone. Furthermore, a subset of RNA binding proteins are attractive drug targets. For example, compounds that are under development as anti-viral targets due to their ability to inhibit RNA helicases could also be tested in novel approaches to medulloblastoma therapy by targeting key RNA binding proteins. In this review, we discuss a number of RNA binding proteins, including Musashi1 (MSI1), DEAD (Asp-Glu-Ala-Asp) box helicase 3 X-linked (DDX3X), DDX31, and cell division cycle and apoptosis regulator 1 (CCAR1), which play potentially critical roles in the growth and/or maintenance of medulloblastoma.

Development of Power Supply Unit for high power GTO driver (대용량 GTO 구동회로용 Power Supply Unit 개발)

  • Cha, J.D.;Yang, H.J.;Hong, S.W.;Lee, H.S.
    • Proceedings of the KIEE Conference
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    • 1996.07a
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    • pp.609-612
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    • 1996
  • This paper describes a design and implementation of the practical SMPS(Switched Mode Power Supply) with multi-output independent regulation scheme. The designed SMPS is applied to the PSU(Power Supply Unit) of high power GTO drivers for a inverter system. In order to accomplish precise voltage regulations for both turn-on and turn-off bias voltages of the GTO driver, the conventional forward type PWM converter scheme is adopted with the Post Regulator using a Saturable Reactor. Analytic design criteria and control schemes are described for practical applications. Finally, the precise regulation of multi-output voltages is proved by experimental results.

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Deubiquitinase USP35 as a novel mitotic regulator via maintenance of Aurora B stability

  • Park, Jinyoung;Song, Eun Joo
    • BMB Reports
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    • v.51 no.6
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    • pp.261-262
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    • 2018
  • Aurora B is an important kinase involved in dynamic cellular events in mitosis. Aurora B activity is controlled by several post-translational modifications (PTMs). Among them, E3 ubiquitin ligase-mediated ubiquitination plays crucial roles in controlling the relocation and degradation of Aurora B. Aurora B, ubiquitinated by different E3 ligases, moves to the exact site for its mitotic function during metaphase-anaphase transition and is then degraded for cell cycle progression at the end of mitosis. However, how the stability of Aurora B is maintained until its degradation has been poorly understood. Recently, we have found that USP35 acts as a deubiquitinating enzyme (DUB) for Aurora B and affects its stability during cell division, thus being involved in the regulation of mitosis. In this review, we discuss the USP35-mediated deubiquitination of Aurora B and the regulation of mitotic progression by USP35.