• Title/Summary/Keyword: Rab10

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Affinity between TBC1D4 (AS160) phosphotyrosine-binding domain and insulin-regulated aminopeptidase cytoplasmic domain measured by isothermal titration calorimetry

  • Park, Sang-Youn;Kim, Keon-Young;Kim, Sun-Min;Yu, Young-Seok
    • BMB Reports
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    • v.45 no.6
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    • pp.360-364
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    • 2012
  • Uptake of circulating glucose into the cells happens via the insulin-mediated signalling pathway, which translocates the glucose transporter 4 (GLUT4) vesicles from the intracellular compartment to the plasma membrane. Rab GTPases are involved in this vesicle trafficking, where Rab GTPases-activating proteins (RabGAP) enhance the GTP to GDP hydrolysis. TBC1D4 (AS160) and TBC1D1 are functional RabGAPs in the adipocytes and the skeletonal myocytes, respectively. These proteins contain two phosphotyrosine-binding domains (PTBs) at the amino-terminus of the catalytic RabGAP domain. The second PTB has been shown to interact with the cytoplasmic region of the insulin-regulated aminopeptidase (IRAP) of the GLUT4 vesicle. In this study, we quantitatively measured the ${\sim}{\mu}M$ affinity ($K_D$) between TBC1D4 PTB and IRAP using isothermal titration calorimetry, and further showed that IRAP residues 1-49 are the major region mediating this interaction. We also demonstrated that the IRAP residues 1-15 are necessary but not sufficient for the PTB interaction.

Icariin promotes melanin synthesis (Icariin의 멜라닌합성 촉진 작용)

  • Cha, Su Bin;Park, Seol A;Kang, Lea Minju;Woo, Won Hong;Mun, Yeun Ja
    • Herbal Formula Science
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    • v.28 no.1
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    • pp.81-90
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    • 2020
  • Objectives : This study was conducted to investigate the effects of major constituents of Epimedium koreanum Nakai (Icariin, epimedium A, epimedium B, and epimedium C) on melanin synthesis. Methods : We measured melanin contents, tyrosinase activity, and expression of Rab27a in B16F10 cells cultured with Epimedium koreanum Nakai ethanol extract (EKN) and their major constituents. After treatment with H89 and dibutyryl cAMP, which inhibit or promote the activation of PKA, we observed changes in melanin synthesis and tyrosinase activity stimulated by EKN. Results : Among them, EKN and icariin enhanced tyrosinase activity and melanin contents. We confirmed that EKN augmented melanin synthesis via cAMP/PKA pathway. Icariin-induced tyrosinase activity and melanin content were attenuated by PKA inhibitor H89, while melanogenic effect of icariin was further augmented by cAMP analog, dbc AMP. However, icariin did not affect the expression of small GTPase Rab27a involved in melanosome transport. Conclusions : These results suggest that icariin promotes melanogenesis through cAMP/PKA pathway but does not affect small GTPase Rab27a.

Hesperidin Suppresses Melanosome Transport by Blocking the Interaction of Rab27A-Melanophilin

  • Kim, Bora;Lee, Jee-Young;Lee, Ha-Yeon;Nam, Ky-Youb;Park, JongIl;Lee, Su Min;Kim, Jin Eun;Lee, Joo Dong;Hwang, Jae Sung
    • Biomolecules & Therapeutics
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    • v.21 no.5
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    • pp.343-348
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    • 2013
  • We investigated the inhibitory effects of hesperidin on melanogenesis. To find melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent.

A Study on the Electricity Distribution Tariff Regulation of Ukraine to Encourage Private Investment on the AMI (AMI 사업에 민간투자를 유인하기 위한 우크라이나 배전서비스 요금정책 연구)

  • Kim, Chul-Nyuon
    • Journal of the Korea Convergence Society
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    • v.12 no.11
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    • pp.19-26
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    • 2021
  • A purpose of this study is to suggest distribution tariff regulation that encourages private investment on the energy efficiency industry of Ukraine. As the electricity market reform and the regulation introduction to encourage energy efficiency are ongoing in Ukraine, it is best time for Korean companies to enter to the market. Therefore, studies on the regulation and the market of Ukraine are required in advance. A simulation of private investment feasibility on AMI business is conducted on one of 32 DSOs in Ukraine. Through the simulation, the directions of RAB tariff regulation, which is the core of the distribution service tariff regulation, were derived. It is essential for DSOs to permit AMI lease assets, introduced by private investors, as regulated assets while other regulations are maintained as it is for investment. This study provides a practical basis by presenting objective data through simulation. It is expected to be helpful for overseas expansion of companies if the study is expanded to the various energy efficiency industries.

Griscelli syndrome type 2: a novel mutation in RAB27A gene with different clinical features in 2 siblings - a diagnostic conundrum

  • Mishra, Kirtisudha;Singla, Shilpy;Sharma, Suvasini;Saxena, Renu;Batra, Vineeta Vijay
    • Clinical and Experimental Pediatrics
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    • v.57 no.2
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    • pp.91-95
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    • 2014
  • Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by cutaneous hypopigmentation, immunodeficiency, and hemophagocytic lymphohistiocytosis. We describe 2 brothers who had GS2 with clinically diverse manifestations. The elder brother presented with a purely neurological picture, whereas the younger one presented with fever, pancytopenia, hepatosplenomegaly, and erythema nodosum. Considering that cutaneous hypopigmentation was a common feature between the brothers, genetic analysis for Griscelli syndrome was performed. As the elder sibling had died, mutation analysis was only performed on the younger sibling, which revealed a novel homozygous mutation in the RAB27A gene on chromosome 15 showing a single-base substitution (c.136T>A p.F46I). Both parents were heterozygous for the same mutation. This confirmed the diagnosis of GS2 in the accelerated phase in both siblings. The atypical features of GS2 in these cases are a novel mutation, isolated neurological involvement in one sibling, association with erythema nodosum, and 2 distinct clinical presentations in siblings with the same genetic mutation.

A Programmable Compensation Circuit for System-on-Chip Application

  • Choi, Woo-Chang;Ryu, Jee-Youl
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.11 no.3
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    • pp.198-206
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    • 2011
  • This paper presents a new programmable compensation circuit (PCC) for a System-on-Chip (SoC). The PCC is integrated with $0.18-{\mu}m$ BiCMOS SiGe technology. It consists of RF Design-for-Testability (DFT) circuit, Resistor Array Bank (RAB) and digital signal processor (DSP). To verify performance of the PCC we built a 5-GHz low noise amplifier (LNA) with an on-chip RAB using the same technology. Proposed circuit helps it to provide DC output voltages, hence, making the RF system chain automatic. It automatically adjusts performance of an LNA with the processor in the SoC when it goes out of the normal range of operation. The PCC also compensates abnormal operation due to the unusual PVT (Process, Voltage and Thermal) variations in RF circuits.

Identification of CEA-interacting proteins in colon cancer cells and their changes in expression after irradiation

  • Yoo, Byong Chul;Yeo, Seung-Gu
    • Radiation Oncology Journal
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    • v.35 no.3
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    • pp.281-288
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    • 2017
  • Purpose: The serum carcinoembryonic antigen (CEA) level has been recognized as a prognostic factor in colorectal cancer, and associated with response of rectal cancer to radiotherapy. This study aimed to identify CEA-interacting proteins in colon cancer cells and observe post-irradiation changes in their expression. Materials and Methods: CEA expression in colon cancer cells was examined by Western blot analysis. Using an anti-CEA antibody or IgG as a negative control, immunoprecipitation was performed in colon cancer cell lysates. CEA and IgG immunoprecipitates were used for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Proteins identified in the CEA immunoprecipitates but not in the IgG immunoprecipitates were selected as CEA-interacting proteins. After radiation treatment, changes in expression of CEA-interacting proteins were monitored by Western blot analysis. Results: CEA expression was higher in SNU-81 cells compared with LoVo cells. The membrane localization of CEA limited the immunoprecipitation results and thus the number of CEA-interacting proteins identified. Only the Ras-related protein Rab-6B and lysozyme C were identified as CEA-interacting proteins in LoVo and SNU-81 cells, respectively. Lysozyme C was detected only in SNU-81, and CEA expression was differently regulated in two cell lines; it was down-regulated in LoVo but up-regulated in SNU-81 in radiation dosage-dependent manner. Conclusion: CEA-mediated radiation response appears to vary, depending on the characteristics of individual cancer cells. The lysozyme C and Rab subfamily proteins may play a role in the link between CEA and tumor response to radiation, although further studies are needed to clarify functional roles of the identified proteins.

Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling

  • Jung, Eun Joo;Chung, Ky Hyun;Kim, Choong Won
    • BMB Reports
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    • v.50 no.9
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    • pp.466-471
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    • 2017
  • The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation.

Inhibitory Effect of Haplamine on Melanosome Transport and Its Mechanism of Action

  • Lee, Kyung Rhim;Myung, Cheol Hwan;Hwang, Jae Sung
    • Korea Journal of Cosmetic Science
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    • v.1 no.1
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    • pp.31-43
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    • 2019
  • Melanosomes are specific melanin-containing intracellular organelles of epidermal melanocytes. In epidermal melanocytes, there are three kinds of key player proteins. Rab27a, melanophilin or Slac2-a and Myosin 5a form a tripartite complex connects the melanosome. Mature melanosomes make movements through the tripartite protein complex along actin filaments.In this study, we found that the haplamine (6-Methoxyflindersine) induced melanosome aggregation around the nucleus in epidermal melanocyte. In an attempt to elucidate the inhibitory effect of haplamine on melanosome transport, effect of haplamineon the expression level of Rab27a, melanophilin and Myosin 5a was measured. The results indicated that haplamine up to 5��M effectively suppressed mRNA and protein expression level of melanophilin.To determine the upstream regulator of melanophilin regulated by haplamine, we checked the level of MITF, c-JUN and USF1. Those are possible transcription factor of melanophilin. Among them,treatment of USF1 siRNA decreased mRNA and protein expression level of USF1 as well as melanophilin. Also, treatment of haplamine decreased mRNA and protein expression level of melanophilin as well as USF1 in a dose-dependent manner. Consequently, we found the inhibitory effect of haplamine on melanosome transport in melan-a melanocyte. Treatment of haplamine reduced melanophilin expression level which is a key protein of melanosome transport. We identified that USF1 could be a major transcription factor of melanophilin regulated by haplamine.