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MKRN1 Induces Degradation of West Nile Virus Capsid Protein by Functioning as an E3 Ligase
Ko, Aram,Lee, Eun-Woo,Yeh, Jung-Yong,Yang, Mi-Ran,Oh, Wonkyung,Moon, Jin-San,Song, Jaewhan American Society for Microbiology 2010 Journal of virology Vol.84 No.1
<B>ABSTRACT</B><P>West Nile virus capsid protein (WNVCp) displays pathogenic toxicity via the apoptotic pathway. However, a cellular mechanism protective against this toxic effect has not been observed so far. Here, we identified Makorin ring finger protein 1 (MKRN1) as a novel E3 ubiquitin ligase for WNVCp. The cytotoxic effects of WNVCp as well as its expression levels were inhibited in U2OS cells that stably expressed MKRN1. Immunoprecipitation analyses revealed an interaction between MKRN1 and WNVCp. Domain analysis indicated that the C terminus of MKRN1 and the N terminus of WNVCp were required for the interaction. MKRN1 could induce WNVCp ubiquitination and degradation in a proteasome-dependent manner. Interestingly, the WNVCp mutant with amino acids 1 to 105 deleted WNVCp was degraded by MKRN1, whereas the mutant with amino acids 1 to 90 deleted was not. When three lysine sites at positions 101, 103, and 104 of WNVCp were replaced with alanine, MKRN1-mediated ubiquitination and degradation of the mutant were significantly inhibited, suggesting that these sites are required for the ubiquitination. Finally, U2OS cell lines stably expressing MKRN1 were resistant to cytotoxic effects of WNV. In contrast, cells depleted of MKRN1 were more susceptible to WNVCp cytotoxicity. Confirming this, overexpression of MKRN1 significantly reduced, but depletion of MKRN1 increased, WNV proliferation in 293T cells. Taken together, our results suggest that MKRN1 can protect cells from WNV by inducing WNVCp degradation.</P>
Ko, Young San,Cho, Sung Jin,Park, Jinju,Kim, Younghoon,Choi, Yong Joon,Pyo, Jung-Soo,Jang, Bo Gun,Park, Jong-Wan,Kim, Woo Ho,Lee, Byung Lan Nature Publishing Group 2015 The British journal of cancer Vol. No.
<P><B>Background:</B></P><P>The biological significance of FOXO1, a member of the forkhead box O transcription factor family, in gastric cancer (GC) remains unclear. The present study provides direct evidence of the role of FOXO1 in tumour growth and metastasis of GC in relation to human epidermal growth factor receptor 2 (HER2).</P><P><B>Methods:</B></P><P>The expressions of FOXO1 and HER2 were modulated in GC cell lines (SNU-638, MKN45, SNU-216 and NCI-N87) by stable transfections. The effects of transfection on GC phenotypes were evaluated <I>in vitro</I> and in animal models. In addition, the relationship between FOXO1 and HER2 was analysed using GC clinical specimens, cell lines and xenografts.</P><P><B>Results:</B></P><P>FOXO1 silencing in GC cells increased colony formation and mesenchymal transition <I>in vitro</I>, as well as tumour growth and metastasis in nude mice, whereas HER2 silencing induced the opposite results.. Furthermore, an inverse relationship between FOXO1 and HER2 was found in clinical specimens of GC, GC cells and GC xenograft tumours. Although a negative crosstalk between these two molecules was shown, double knockdown of both FOXO1 and HER2 in GC cells revealed that HER2 silencing reversed the FOXO1 shRNA-induced migration and invasion even without the FOXO1 restoration.</P><P><B>Conclusions:</B></P><P>Our results indicate that loss of FOXO1 promotes GC growth and metastasis by upregulating HER2 expression and that the HER2 expression is more critical to the induction of GC cell metastasis. The present study provides evidence that the FOXO1/HER2 pathway may regulate GC progression in a subgroup of GC patients.</P>
등속성 보강 트레이닝시 대퇴부 근력발현 및 최대 근려발휘각의 변화
장용우(Yong Woo Jang),권양기(Yang Ki Kwon),서충진(Chung Jin Seo),고영완(Young Wan Ko),이동욱(Dong Wok Lee),송문석(Mun Suk Song),이채산(Chae San Lee),이광호(Kwang Ho Lee) 한국사회체육학회 2001 한국사회체육학회지 Vol.16 No.-
The purpose of this study was to analyze for changes of thigh strength revelation and peak touqre angle during isokinetic exercise in each angle velocity. Subjects were classify to low velocity exercise(8) and medium velocity exercise(7). They were measured and evaluated to the strength and peak torque angle in each angle velocity by isokinetic exercise during 4 weeks through kin-corn The finding of this study were as follows: 1. Extension strength in each angle velocity show high in the low velocity to L·V·G and medium velocity to M·V·G, but significant increment of strength showed at low velocity 30˚/sec and 90˚/sec(p<.05). Also, flexsion strength showed high in the low velocity to L·V·G and medium velocity to M·V·G, but significant increment of strength showed at low velocity 60˚/sec and medium velocity 150˚/sec, 180˚/sec(p<.05). 2. Peak torque angle at extension showed a significant different at medium velocity 150˚/sec and 180˚/sec between two group in each angle velocity(p<.05). Peak torque angle during exercise duration in each group showed a significant high increment at low velocity 60˚/sec and medium velocity 150˚/sec, 180˚/sec(p<.05). Peak torque angle at extension showed a significant different at all test velocity with the exception of 30 ° /sec, 180 ° /sec between two group in each angle velocity(p<.05, p<.001). Peak torque angle during exercise duration in each group showed a significant high increment at all test velocity with the exception of 60˚/sec(p<.05, p<.01). Within the scope of this study, for the greatest to strength increment during short duration and all range of thigh muscle contraction make judgment be effective to training execution of medium velocity than low velocity.