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Deubiquitination and Stabilization of PD-L1 by CSN5
Lim, Seung-Oe,Li, Chia-Wei,Xia, Weiya,Cha, Jong-Ho,Chan, Li-Chuan,Wu, Yun,Chang, Shih-Shin,Lin, Wan-Chi,Hsu, Jung-Mao,Hsu, Yi-Hsin,Kim, Taewan,Chang, Wei-Chao,Hsu, Jennifer L.,Yamaguchi, Hirohito,Ding Elsevier 2016 Cancer cell Vol.30 No.6
<P><B>Summary</B></P> <P>Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TNF-α stabilizes cancer cell PD-L1 in response to chronic inflammation </LI> <LI> Activation of NF-κB by TNF-α induces CSN5 expression leading to PD-L1 stabilization </LI> <LI> CSN5 enzyme activity controls T cell suppression via PD-L1 deubiquitination </LI> <LI> Destabilization of PD-L1 by CSN5 inhibitor curcumin benefits anti-CTLA4 therapy </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Lin Zhao,Peng-fei Li,Chun-hua Lu,Shu-guang Li,Yue-mao Shen,Yue-zhong Li 한국미생물학회 2010 The journal of microbiology Vol.48 No.4
3-O-α-D-ribofuranosyl epothilone A (epothiloneoside A) is a major component of glycosylated epothilones in Sorangium cellulosum strain So0157-2. The production and glycosylation ratios of epothiloneoside A in both solid and liquid culture conditions with various pH values and carbon sources were studied. The results showed that glycosylation occurs whenever epothilones are produced, regardless of changes in pH values,production time curves, and different carbon sources. We suggest that glycosylation is a stable process,paralleling the biosynthesis of epothilones in the So0157-2 strain.
Mao-lin Li,Han-min Gu,Hong-ya Hang,Yao-li Jiang,Jiao Jiang,Qian-na Gu,Wen-yan Wu,M.-L. Li 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.4
Radix ranunculus temate saponins (RRTS), one of the main constituents extracted from the popular traditional Chinese medicine Radix Ranunculi ternati, has been reported to have various biological activities including anti-cancer effect. The aim of this study is to investigate the effect of RRTS on the cell proliferation and apoptosis in human gastric adenocarcinoma SGC-7901 cells. The data showed that exposure to RRTS for 24 h produced cytotoxic effects on SGC- 7901 cells in a dose-dependent manner (with an IC50 value of 21.22±2.76 μg/mL), which was accompanied by apoptosis induction (from 2.18±0.89% (control) to 63.72±13.16% (100 μg/mL)). Both the extrinsic or death receptor pathway and the intrinsic or mitochondrial pathway were involved in RRTS-induced apoptosis in SGC-7901 cells. Furthermore, apoptotic signaling induced by RRTS was amplified by cross-link between the two pathways via the signal-integrating protein Bid. In conclusion, our findings contribute to better understanding the molecular mechanism of RRTS’ effect on gastric cancer cells and form the basis of the therapeutic development of RRTS in treating gastric cancer in the future.
Knockout of the EgriBLOS2 gene results in the transparent integuments of Ectropis grisescens larvae
Li Jia-Li,Zhuang Xiang-Lin,Yuan Ting-Ting,Cai Xiao-Ming,Luo Zong-Xiu,Bian Lei,Chen Zong-Mao,Li Zhao-Qun,Liu Nai-Yong 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.1
The body colors of insects have evolved specialized roles in body protection, signaling and physiology. In some case, the larvae can camouflage their body colors to adapt the habitants and protect themselves. However, the genetic and molecular basis on larval body colors of the tea geometrid, Ectropis grisescens, remains poorly known. Here, we reported an effect of the lysosome-related organelles complex-1, subunit 2 (EgriBLOS2) gene knockout on larval integuments of E. grisescens, by using a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Combining transcriptomic data and PCR approaches, we first identified the EgriBLOS2 gene from E. grisescens, which encoded 137 amino acids and comprised 3 introns. In the phylogenetic analysis, EgriBLOS2 clustered in the Lepidoptera clade with high conservation to members in other lepidopteran species. Developmental expression profiles revealed that EgriBLOS2 was constantly tran scribed at each stage, in which its expression was significantly lower in 2nd instar larvae than that of other instars. After injecting EgriBLOS2-specific guide RNA and Cas9 messenger RNA into eggs, 70% of larvae showed the translucent integuments in G0 generation, with an emphasis on black splayed patterns in the 2nd and 8th segments of abdomens. However, some typical characteristics of larvae were not obviously changed in mutant instars, such as ocelli, mouthparts and other appendants. This study has unraveled the roles of EgriBLOS2 in the formation of larval integument colors, and provides an alternative strategy for pest management based on the colors in this species.
Mao, Ye-Qing,Xu, Xin,Lin, Yi-Wei,Chen, Hong,Hu, Zheng-Hui,Xu, Xiang-Lai,Zhu, Yi,Wu, Jian,Zheng, Xiang-Yi,Qin, Jie,Xie, Li-Ping Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12
Insulin-like growth factor-binding protein-3 (IGFBP3) has been identified as a putative tumor suppressor with multifunctional roles in the IGF axis. Recently, there have been a growing body of studies investigating the relation between the IGFBP3 A-202C polymorphism, circulating IGFBP3 and prostate cancer risk, but their outcomes varied leading to controversy. Hence, it is necessary to perform a meta-analysis covering all eligible studies to shed a light on the association of IGFBP3 A-202C and cancer risk. Finally, we included a total of 11 relevant articles between 2003 and 2010 covering 14 case-control studies including 9,238 cases and 8,741 controls for our analysis. Our results showed that A-202C was a marginal risk factor of prostate cancer (allele contrast: OR=1.08, 95% CI :1.01-1.16; dominant model: OR=1.11, 95% CI :1.01-1.22; heterozygote codominant model: OR=1.11, 95% CI :1.03-1.18; homozygote contrast: OR=1.19, 95% CI :1.03-1.37). Stratification analysis revealed that sample size and control source were two major heterogeneous meta-factors especially in the recessive model (source: Population-based control group :p=0.30,I2=16.7%, Hospital-based control group: p=0.20, I2=30.3%; sample size: Small: p=0.22,I2= 32.8%, Medium: p=0.09,I2=48%, Large p=0.60,I2=0.0%); However, contrary to previous findings, no significance was found in racial subgroups. No significant publication bias was found in our analysis. Considering the robustness of the results and the discrepancy among some studies, there might be some unsolved confounding factors, and further more critical large studies are needed for confirmation.
Mao-feng Yue,Ren-chao Zhou,Ye-lin Huang,Guo-rong Xin,Su-hua Shi,Li Feng 한국식물학회 2010 Journal of Plant Biology Vol.53 No.2
High levels of genetic variation enable species to adapt to changing environments and provide plant breeders with the raw materials necessary for artificial selection. In the present study, six AFLP primer pairs were used to assess the genetic diversity of Desmodium triflorum (L.)DC. from 12 populations in South China. A high percentage of polymorphic loci (P=76.16%) and high total gene diversity (HT=0.310) were found, indicating that the genetic diversity of D. triflorum is high at the species level. Genetic diversity was also relatively high at the population level (P=55.85%, He=0.230). The coefficient of gene differentiation among populations (GST) was 0.255, indicating that while most genetic diversity resided within populations, there was also considerable differentiation among populations. AMOVA also indicated 24.29% of the total variation to be partitioned among populations (ΦST=0.243). UPGMA clustering analysis based on genetic distances showed that the 12 populations could be separated into three subgroups: an eastern, a western, and a central-southern subgroup. However, a Mantel test revealed no significant correlation (r=0.286, p=0.983)between the geographical distances and genetic distances separating these populations; mountain barriers to gene flow and human disturbance may have confounded these correlations. The present study has provided some fundamental genetic data that will be of use in the exploitation of D. triflorum.
Mao Lin,Ying-Hui Li,Liang Qu,Chen Wu,Guo-Qiang Yuan 전력전자학회 2016 JOURNAL OF POWER ELECTRONICS Vol.16 No.1
Fault detection is the research focus and priority in this study to ensure the high reliability of a proposed three-level inverter. Kernel principal component analysis (KPCA) has been widely used for feature extraction because of its simplicity. However, highlighting useful information that may be hidden under retained KPCs remains a problem. A weighted KPCA is proposed to overcome this shortcoming. Variable contribution plots are constructed to evaluate the importance of each KPC on the basis of sensitivity analysis theory. Then, different weighting values of KPCs are set to highlight the useful information. The weighted statistics are evaluated comprehensively by using the improved feature eigenvectors. The effectiveness of the proposed method is validated. The diagnosis results of the inverter indicate that the proposed method is superior to conventional KPCA.
THE (R,S)-SYMMETRIC SOLUTIONS TO THE LEAST-SQUARES PROBLEM OF MATRIX EQUATION AXB = C
Mao-lin Liang,Li-fang Dai,San-fu Wang 한국전산응용수학회 2009 Journal of applied mathematics & informatics Vol.27 No.5
For real generalizedreflexive matrices R, S, i.e., RT = R, R2 = I, ST = S, S2 = I, we say that real matrix X is (R,S)-symmetric, if RXS = X. In this paper, an iterative algorithm is proposed to solve the least-squares problem of matrix equation AXB = C with (R,S)-symmetric X. Furthermore, the optimal approximation solution to given matrix X0 is also derived by this iterative algorithm. Finally, given numerical example and its convergent curve show that this method is feasible and efficient. For real generalizedreflexive matrices R, S, i.e., RT = R, R2 = I, ST = S, S2 = I, we say that real matrix X is (R,S)-symmetric, if RXS = X. In this paper, an iterative algorithm is proposed to solve the least-squares problem of matrix equation AXB = C with (R,S)-symmetric X. Furthermore, the optimal approximation solution to given matrix X0 is also derived by this iterative algorithm. Finally, given numerical example and its convergent curve show that this method is feasible and efficient.