• Title/Summary/Keyword: Smurf2

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Protein Arginine Methyltransferase 1 Methylates Smurf2

  • Cha, Boksik;Park, Yaerin;Hwang, Byul Nim;Kim, So-young;Jho, Eek-hoon
    • Molecules and Cells
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    • v.38 no.8
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    • pp.723-728
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    • 2015
  • Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-${\beta}$ signaling by targeting Smads and TGF-${\beta}$ receptor. However, the regulatory mechanism of Smurf2 has not been elucidated. Arginine methylation is a type of post-translational modification that produces monomethylated or dimethylated arginine residues. In this report, we demonstrated methylation of Smurf2 by PRMT1. In vitro methylation assay showed that Smurf2, not Smurf1, was methylated by PRMT1. Among the type I PRMT family, only PRMT1 showed activity for Smurf2. Transiently expressed Smurf2 was methylated by PRMT1, indicating Smurf2 is a novel substrate of PRMT1. Using deletion constructs, methylation sites were shown to be located within amino acid region 224-298 of Smurf2. In vitro methylation assay following point mutation of putative methylation sites confirmed the presence of Arg232, Arg234, Arg237, and Arg239. Knockdown of PRMT1 resulted in increased Smurf2 expression as well as inhibition of TGF-${\beta}$-mediated reporter activity. Although it is unclear whether or not increased Smurf2 expression can be directly attributed to lack of methylation of arginine residues, our results suggest that methylation by PRMT1 may regulate Smurf2 stability and control TGF-${\beta}$ signaling.

Opposing Effects of Arkadia and Smurf on TGFβ1-induced IgA Isotype Expression

  • Choi, Seo-Hyun;Seo, Goo-Young;Nam, Eun-Hee;Jeon, Seong-Hyun;Kim, Hyun-A;Park, Jae-Bong;Kim, Pyeung-Hyeun
    • Molecules and Cells
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    • v.24 no.2
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    • pp.283-287
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    • 2007
  • $TGF-{\beta}1$ induces Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent class switching recombination (CSR) to IgA. In the present study, we investigated the roles of two E3-ubiquitin ligases, Smurfs (HECT type) and Arkadia (RING finger type) on $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Smurf1 and Smurf2 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Further, over-expression of Smurf1 and Smurf2 decreased both Smad3/4-mediated and Runx3-mediated $GL{\alpha}$ promoter activities, suggesting that the Smurfs can down-regulate the major $TGF-{\beta}1$ signaling pathway and decrease $GL{\alpha}$ gene expression. In parallel, the over-expressed Smurf1 decreased the expression of endogenous IgA CSR-predictive transcripts ($GLT_{\alpha}$, $PST_{\alpha}$, and $CT_{\alpha}$) and also $TGF{\beta}1$-induced IgA secretion. Conversely over-expression of Arkadia abolished the inhibitory effect of Smad7 on $TGF{\beta}1$-induced $GLT_{\alpha}$ expression and IgA secretion. Similar results were obtained in the presence of over-expressed Smad7 and Smurf1. These results indicate that Arkadia can amplify $TGF{\beta}1$-induced IgA CSR by degrading Smad7, which interacts with Smurf1. We conclude that Smurf and Arkadia have opposite roles in the regulation of $TGF{\beta}1$-induced IgA isotype expression.

Beta-Catenin Downregulation Contributes to Epidermal Growth Factor-induced Migration and Invasion of MDAMB231 Cells

  • Kwon, Arang;Park, Hyun-Jung;Baek, Jeong-Hwa
    • International Journal of Oral Biology
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    • v.43 no.3
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    • pp.161-169
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    • 2018
  • We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.

A Dynamic Update Engine of IPS for a DoS Attack Prevention of VoIP (VoIP의 DoS공격 차단을 위한 IPS의 동적 업데이트엔진)

  • Cheon, Jae-Hong;Park, Dea-Woo
    • KSCI Review
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    • v.14 no.2
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    • pp.235-244
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    • 2006
  • This paper attacked the unknown DoS which mixed a DoS attack, Worm and the Trojan horse which used IP Source Address Spoofing and Smurf through the SYN Flooding way that UDP, ICMP, Echo, TCP Syn packet operated. the applications that used TCP/UDP in VoIP service networks. Define necessity of a Dynamic Update Engine for a prevention, and measure Miss traffic at RT statistics of inbound and outbound parts in case of designs of an engine at IPS regarding an Self-learning module and a statistical attack spread. and design a logic engine module. Three engines judge attack grades (Attack Suspicious, Normal), and keep the most suitable filtering engine state through AND or OR algorithms at Footprint Lookup modules. A Real-Time Dynamic Engine and Filter updated protected VoIP service from DoS attacks, and strengthened Ubiquitous Security anger, and were turned out to be.

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A Study on the Analysis of Uncanny of 3D Animation Originated from 2D Animation (2D애니메이션을 원작으로 하는 3D애니메이션의 Uncanny현상에 대한 연구)

  • Bae, sun cheol;Choi, dong-hyuk
    • Proceedings of the Korea Contents Association Conference
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    • 2015.05a
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    • pp.83-84
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    • 2015
  • 최근 개봉하는 영화들을 살펴보면 2D Animation이었던 작품들이 3D Animation으로 제작되고 있다. 먼저 1981년 미국 NBC에서 방영된 후 2011년과 2013년에 실사합성 Animation으로 개봉된 'The Smurf'가 있고, 1999년 'Nickelodeon Kids' Choice Awards'에서 처음 방영되어 2015년 2월에 실사합성 Animation으로 극장에 개봉한 'The SpongeBob Movie: Sponge Out of Water'이 있다. 과거 만화책과 TV에서 방영되어 아주 큰 호응을 받은 작품들을 기억하는 관객들에게는 3D Animation에서 만들어지는 3D의 공간감과 입체감이 보는 관객들로 하여금 이질감을 느낄 수 있다. 본 논문은 이러한 이질감을 프로이트의 논문 '두려운 낯설음'에서 이야기한 Uncanny현상에 대입한다. 2D Animation이 원작인 작품을 3D Animation으로 만드는 데는 적지 않은 어려움이 있고 각 작품들만의 특징이 있기 때문에, 본 연구를 통해서 2D Animation을 원작으로 하는 3D Animation작품에서 감상하는 관객들로 하여금 이질감을 느끼는 Uncanny현상이 작품에 미치는 영향 대한 연구 결과를 도출하고자 한다.

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Modeling and Simulation of Firewall System and Security Functions of Operating System for Network Security (네트워크 보안을 위한 침입차단 시스템과 운영체제 보안 기능 모델링 및 시뮬레이션)

  • 김태헌;이원영;김형종;김홍근;조대호
    • Journal of the Korea Society for Simulation
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    • v.11 no.2
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    • pp.1-16
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    • 2002
  • The need for network security is being increasing due to the development of information communication and internet technology. In this paper, firewall models, operating system models and other network component models are constructed. Each model is defined by basic or compound model, referencing DEVS formalism. These models and the simulation environment are implemented with MODSIM III, a general purpose, modular, block-structured high-level programming language which provides direct support for object-oriented programming and discrete-event simulation. In this simulation environment with representative attacks, the following three attacks are generated, SYN flooding and Smurf attack as an attack type of denial of service, Mail bomb attack as an attack type of e-mail. The simulation is performed with the models that exploited various security policies against these attacks. The results of this study show that the modeling method of packet filtering system, proxy system, unix and windows NT operating system. In addition, the results of the simulation show that the analysis of security performance according to various security policies, and the analysis of correlation between availability and confidentiality according to security empowerment.

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