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Differential regulation of p53 and p21 by MKRN1 E3 ligase controls cell cycle arrest and apoptosis.
Lee, Eun-Woo,Lee, Min-Sik,Camus, Suzanne,Ghim, Jaewang,Yang, Mi-Ran,Oh, Wonkyung,Ha, Nam-Chul,Lane, David P,Song, Jaewhan Published for the European Molecular Biology Organ 2009 The EMBO journal Vol.28 No.14
<P>Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. Interestingly, MKRN1 used earlier unknown sites, K291 and K292, for p53 ubiquitination and subsequent degradation. Under severe stress conditions, however, MKRN1 primarily induced the efficient degradation of p21. This regulatory process contributed to the acceleration of DNA damage-induced apoptosis by eliminating p21. MKRN1 depletion diminished adriamycin or ultraviolet-induced cell death, whereas ectopic expression of MKRN1 facilitated apoptosis. Furthermore, MKRN1 stable cell lines that constantly produced low levels of p53 and p21 exhibited stabilization of p53, but not p21, with increased cell death on DNA damage. Our results indicate that MKRN1 exhibits dual functions of keeping cells alive by suppressing p53 under normal conditions and stimulating cell death by repressing p21 under stress conditions.</P>
Kö,nig, Alexander,Yang, Jaewon,Jo, Eunji,Park, Kyu Ho Paul,Kim, Hyun,Than, Thoa Thi,Song, Xiyong,Qi, Xiaoxuan,Dai, Xinghong,Park, Soonju,Shum, David,Ryu, Wang-Shick,Kim, Jung-Hee,Yoon, Seung Kew,P Elsevier 2019 Journal of hepatology Vol.71 No.2
<P><B>Background & Aims</B></P> <P>As hepatitis B virus (HBV) spreads through the infected liver it is simultaneously secreted into the blood. HBV-susceptible <I>in vitro</I> infection models do not efficiently amplify viral progeny or support cell-to-cell spread. We sought to establish a cell culture system for the amplification of infectious HBV from clinical specimens.</P> <P><B>Methods</B></P> <P>An HBV-susceptible sodium-taurocholate cotransporting polypeptide-overexpressing HepG2 cell clone (HepG2-NTCPsec+) producing high titers of infectious progeny was selected. Secreted HBV progeny were characterized by native gel electrophoresis and electron microscopy. Comparative RNA-seq transcriptomics was performed to quantify the expression of host proviral and restriction factors. Viral spread routes were evaluated using HBV entry- or replication inhibitors, visualization of viral cell-to-cell spread in reporter cells, and nearest neighbor infection determination. Amplification kinetics of HBV genotypes B-D were analyzed.</P> <P><B>Results</B></P> <P>Infected HepG2-NTCPsec+ secreted high levels of large HBV surface protein-enveloped infectious HBV progeny with typical appearance under electron microscopy. RNA-seq transcriptomics revealed that HBV does not induce significant gene expression changes in HepG2-NTCPsec+, however, transcription factors favoring HBV amplification were more strongly expressed than in less permissive HepG2-NTCPsec−. Upon inoculation with HBV-containing patient sera, rates of infected cells increased from 10% initially to 70% by viral spread to adjacent cells, and viral progeny and antigens were efficiently secreted. HepG2-NTCPsec+ supported up to 1,300-fold net amplification of HBV genomes depending on the source of virus. Viral spread and amplification were abolished by entry and replication inhibitors; viral rebound was observed after inhibitor discontinuation.</P> <P><B>Conclusions</B></P> <P>The novel HepG2-NTCPsec+ cells efficiently support the complete HBV life cycle, long-term viral spread and amplification of HBV derived from patients or cell culture, resembling relevant features of HBV-infected patients.</P> <P><B>Lay summary</B></P> <P>Currently available laboratory systems are unable to reproduce the dynamics of hepatitis B virus (HBV) spread through the infected liver and release into the blood. We developed a slowly dividing liver-derived cell line which multiplies infectious viral particles upon inoculation with patient- or cell culture-derived HBV. This new infection model can improve therapy by measuring, in advance, the sensitivity of a patient’s HBV strain to specific antiviral drugs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cell culture system that mimicks complete HBV life cycle from entry to egress. </LI> <LI> Efficient <I>in vitro</I> infection with crude HBV patient sera. </LI> <LI> Up to 50- and 1,300-fold net amplification of patient- and cell culture-derived input HBV in the supernatant. </LI> <LI> Polyethylene glycol-independent HBV spread to adjacent cells, forming infected cell clusters. </LI> <LI> Evaluation of patient- and cell culture-derived HBV amplification w/wo antivirals over 8 weeks. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Fang, Baizeng,Kim, Min-Sik,Kim, Jung Ho,Song, Min Young,Wang, Yan-Jie,Wang, Haijiang,Wilkinson, David P.,Yu, Jong-Sung Royal Society of Chemistry 2011 Journal of materials chemistry Vol.21 No.22
<P>A very efficient, reproducible approach has been developed to fabricate a multiwall carbon nanotube (MWCNT)-supported, high Pt loading electrocatalyst. In this strategy, MWCNT was first functionalized with an anionic surfactant, sodium dodecylsulfate (SDS), to enhance the hydrophilicity of the MWCNTs for high Pt loading. The SDS-modified MWCNTs were further used to support high loading of Pt nanoparticles (NPs) through a urea-assisted homogeneous deposition (HD) strategy, followed by reduction using ethylene glycol (EG) as the precursor of a reducing agent. Through the input of SDS on the MWCNTs, Pt complex species can be readily anchored on the outer surface of the MWCNTs, while <I>in situ</I> pH adjustment of the solution with urea and reduction by EG enable the Pt NPs to disperse very uniformly on the SDS–MWCNT support with small particles size. Due to its unique structural characteristics, such as high electronic conductivity, the one-dimensional nanotube structure favouring fast electron transfer and more uniform Pt NP dispersion on the support with smaller particle size, the SDS-MWCNT-supported Pt (60 wt%) catalyst considerably outperformed a commercially available Johnson Matthey catalyst with the same Pt loading supported on Vulcan carbon black, when they were each employed as a cathode catalyst in proton exchange membrane fuel cells.</P> <P>Graphic Abstract</P><P>Non-covalent functionalization of MWCNT by SDS gives high density anchoring of Pt(<SMALL>IV</SMALL>) species, while an EG homogeneous reduction allows a small metal particle size, resulting in greatly improved PEMFC performance for SDS–MWCNT-supported Pt cathode catalysts. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1jm10847f'> </P>
노면 가진으로부터 차체로 전달되는 구조기인 힘 측정장비에 대한 연구
강연준(Yeon Jun Kang),David P. Song,민동우(Dongwoo Min) 한국소음진동공학회 2015 한국소음진동공학회 학술대회논문집 Vol.2015 No.10
The primary purpose of this study is to verify the suspension force rig which is developed for structure-borne road noise analysis prior to availability of vehicle boy. With Continuous increase market of hybrid and electrical vehicle, NVH engineers endeavor to improve vehicle road noise thoroughly. However, tackling the vehicle road noise is known for one of the most difficult NVH issue until now because NVH engineers and R&H engineers must reach a compromise between quieter interior noise and crisp handling. To achieve such, identifying the body input force is crucial and thus, a suspension rig which enables direct force measurement has developed. In this paper, the suspension rig is verified through a comparative analysis with the actual baseline vehicle measureme nt with varying tire pressure, rig mass, and suspension parameters up to 300 Hz.
차대 동력계에서 자동차 구속조건에 따른 거동 특성 비교
강연준(Yeon Jun Kang),김희수(Heesoo Kim),David P. Song,민동우(Dongwoo Min) 한국소음진동공학회 2014 한국소음진동공학회 학술대회논문집 Vol.2014 No.10
The primary purpose of this study is to observe the dynamic behavior within a vehicle on chassis dynamometer throughout cleat impact testing with two different constraining setups (Tie-down strap and one point fixation). Throughout this empirical experiment, no outstanding dynamic behavior characteristics are observed between two setups and thus, the performance of the one point fixation device is validated. Neither the interior noise nor acceleration at driver seat rail and knuckle is heavily influenced by two different constraining methods. However, one point fixation is far more advantageous considering its shorter set up time and its capability of measuring traction force with its built in force sensor.
Transmissibility를 이용한 Input Boundary 변화에 따른 차량 시스템의 Characteristic에 대한 연구
강연준(Yeonjune Kang),김준구(Jungu Kim),송현진(David P. Song),민동우(Dongwoo Min) 한국소음진동공학회 2015 한국소음진동공학회 학술대회논문집 Vol.2015 No.10
The purpose of this study is to apply and experimentally verify the concept of the transmissibility on the vehicle system. In the study, the concept of transmissibility is applied to the vehicle cabin sound pressure and acceleration data at the knuckle of suspension. Furthermore, the systems’s transmissibility characteristics of the system are experimentally analyzed by replacing wheels and tires of a vehicle. It is also proved by the research that the transmissibility properties of the system does not change, although the input boundary of the system is changed. Additionally, the study suggests that transmissibility can be one of the parameters for evaluating the behavior of the system.
강연준(Yeon Jun Kang),민동우(Dongwoo Min),송현진(David P. Song),김형건(Hyoung Gun Kim),조문환(Munhwan Cho) 한국소음진동공학회 2015 한국소음진동공학회 학술대회논문집 Vol.2015 No.4
The purpose of this study is to optimize the acceleration operational data at suspension link pivotal point for Transfer Path Analysis (TPA). Generally, acceleration signal obtained at pivotal point contains not only fore-aft, radial, and tangential direction component but also undesirable rotational signal. An experimental approach to eliminate undesirable rotational signal is studied by adding extra accelerometer on the opposite side of where the original pivotal point acceleration is obtained. The acceleration signals at suspension link pivotal point are compared to one another then, averaged with phase. This averaged acceleration spectrum is then validated through TPA results.
가속도계 위치 변경에 따른 현가장치 TPA 개선에 대한 연구
강연준(YeonJune Kang),김준구(Jun-gu Kim),민동우(Dong-woo Min),송현진(David P. Song),이강덕(Kang-duk Ih) 한국소음진동공학회 2016 한국소음진동공학회 학술대회논문집 Vol.2016 No.4
This study is about how to improve accuracy when Transfer Path Analysis (TPA) is applied to a multi-link vehicle suspension. TPA is generally employed to estimate road noise and NVH of a vehicle suspension. In this case, however, TPA has some spatial constraints on suspension system. To put it another way, there is no room for sensor attachment and excitation because of its compact structure. Therefore, the inaccurate setting of the sensor and excitation, which is potentially problematic, could not acquire high reliability on Frequency Response Function (FRF) with accuracy and consistence. To deal with the obstacles, the experiment was conducted by locating an accelerometer between linkages or arms and bushes, which connect them to a sub-frame, on the way of energy transfer from road vibration. Also, using TPA with the data on acceleration from the placement of accelerometer to the target at the mounting point of the sub-frame, this study compares the result of this new approach with that of the existing TPA and identifies its efficiency.