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111.
Compartment‐specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition 下载免费PDF全文
Annett Neuner Mohamed YH Mohamed D Lys Guilbride Karsten Richter Michael Lisby Elmar Schiebel Axel Mogk Bernd Bukau 《The EMBO journal》2015,34(6):778-797
Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins in the cytosol of eukaryotic cells partition between cytosolic juxtanuclear (JUNQ) and peripheral deposits. Substrate ubiquitination acts as the sorting principle determining JUNQ deposition and subsequent degradation. Here, we show that JUNQ unexpectedly resides inside the nucleus, defining a new intranuclear quality control compartment, INQ, for the deposition of both nuclear and cytosolic misfolded proteins, irrespective of ubiquitination. Deposition of misfolded cytosolic proteins at INQ involves chaperone‐assisted nuclear import via nuclear pores. The compartment‐specific aggregases, Btn2 (nuclear) and Hsp42 (cytosolic), direct protein deposition to nuclear INQ and cytosolic (CytoQ) sites, respectively. Intriguingly, Btn2 is transiently induced by both protein folding stress and DNA replication stress, with DNA surveillance proteins accumulating at INQ. Our data therefore reveal a bipartite, inter‐compartmental protein quality control system linked to DNA surveillance via INQ and Btn2. 相似文献
112.
Li‐Fei Bai Hua Zhao Cheng‐Yi Tang Yan‐Jun Pang Rong‐Wu Yang Xiao‐Ming Wang Gui‐Hua Lu Yong‐Hua Yang 《Chirality》2015,27(3):274-280
In this study, a shikonin ester derivative, compound 3g , was selected to evaluate its anticancer activities and we found that compound 3g exhibited better antitubulin activities against the human HepG2 cell line with an IC50 value of 1.097 μM. Furthermore, the inhibition of tubulin polymerization results indicated that compound 3g demonstrated the most potent antitubulin activity (IC50 = 13.88), which was compared with shikonin and colchicine as positive controls (IC50 = 25.28 μM and 22.56 μM), respectively. Compound 3g was simulated to have good binding site with tubulin and arrested the cell cycle at G2/M phase, which also induces apoptosis in HepG2 cells, in which P53 and members of Bcl‐2 protein family were both involved in the progress of apoptosis revealed by western blot. Confocal microscopy observations revealed compound 3g targeted tubulin and altered its polymerization by interfering with microtubule organization. Based on these results, compound 3g functions as a potent anticancer agent targeting tubulin. Chirality 27:274–280, 2015.. © 2015 Wiley Periodicals, Inc. 相似文献
113.
Longbiao Guo Jie Qiu Zujing Han Zihong Ye Chao Chen Chuanjun Liu Xiufang Xin Chu‐Yu Ye Ying‐Ying Wang Hongqing Xie Yu Wang Jiandong Bao She Tang Jie Xu Yijie Gui Fei Fu Weidi Wang Xingchen Zhang Qianhua Zhu Xuanmin Guang Chongzhi Wang Haifeng Cui Daguang Cai Song Ge Gerald A. Tuskan Xiaohan Yang Qian Qian Sheng Yang He Jun Wang Xue‐Ping Zhou Longjiang Fan 《The Plant journal : for cell and molecular biology》2015,83(4):600-609
114.
Gui Yang Xiao-Rui Geng Zhi-Qiang Liu Jiang-Qi Liu Xiao-Yu Liu Ling-Zhi Xu Huan-Ping Zhang Ying-Xue Sun Zhi-Gang Liu Ping-Chang Yang 《The Journal of biological chemistry》2015,290(20):12858-12867
Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy. 相似文献
115.
116.
Androgen receptor binding to an androgen‐responsive element in the promoter of the Srsf4 gene inhibits its expression in mouse Sertoli cells 下载免费PDF全文
117.
Xu Han Lixuan Gui Bing Liu Jing Wang Yaru Li Xiayun Dai Jun Li Binyao Yang Gaokun Qiu Jing Feng Xiaomin Zhang Tangchun Wu Meian He 《BMC genetics》2015,16(1)
Background
Multiple studies investigated the associations between serum uric acid and coronary heart disease (CHD) risk. However, further investigations still remain to be carried out to determine whether there exists a causal relationship between them. We aim to explore the associations between genetic variants in uric acid related loci of SLC2A9 and ABCG2 and CHD risk in a Chinese population.Results
A case–control study including 1,146 CHD cases and 1,146 controls was conducted. Association analysis between two uric acid related variants (SNP rs11722228 in SLC2A9 and rs4148152 in ABCG2) and CHD risk was performed by logistic regression model. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Compared with subjects with A allele of rs4148152, those with G allele had a decreased CHD risk and the association remained significant in a multivariate model. However, it altered to null when BMI was added into the model. No significant association was observed between rs11722228 and CHD risk. The distribution of CHD risk factors was not significantly different among different genotypes of both SNPs. Among subjects who did not consume alcohol, the G allele of rs4148152 showed a moderate protective effect. However, no significant interactions were observed between SNP by CHD risk factors on CHD risk.Conclusions
There might be no association between the two uric acid related SNPs with CHD risk. Further studies were warranted to validate these results.Electronic supplementary material
The online version of this article (doi:10.1186/s12863-015-0162-7) contains supplementary material, which is available to authorized users. 相似文献118.
Yue Xiao Yu Zhang Bin Jiang Dan Dan Liu Yan Juan Niu Tian Gui 《World journal of microbiology & biotechnology》2011,27(9):2147-2153
A new alkaline keratinase, which could kill Meloidogyne incognita (a root-knot nematode) was separated and purified from Bacillus sp. 50-3 in this study. The solid ammonium sulfate was selected to precipitate the enzyme and its proper adding mass was
also determined. After solid ammonium sulfate precipitation and liquid chromatography on DEAE-Sephadex-A50 column, there was
17.7-fold purification with a yield of 46.5%, as determined by azokeratin as substrate. The purification effect was determined
through SDS-PAGE and the molecular weight of the enzyme was found to be 27,423 Da by the MALDI-TOF-MS. When the second-stage
juveniles of Meloidogyne incognita were exposed to 50 μg/ml of keratinase solution, 98.5% of Meloidogyne incognita mortality rates were obtained compared to control after 24 h. Its simple purification step and high yield from the cheap
medium affords this keratinase great biotechnological potential, especially in controlling root-knot nematodes such as Meloidogyne incognita. To the best of our knowledge, this study is the first report that uses keratinase as a pesticide. 相似文献
119.
A novel quantum dots (QDs) based biosensor was developed to monitor physiological pH changes in both fixed and living cells by means of pH-dependent emission color of the QDs. In our system, the nominally single-sized colloidal solution samples of the L-cysteine-capped CdTe QDs with intrinsically broadened size distributions were prepared by employing aqueous synthesis technique. The quench of fluorescence intensities of the QDs with a 16 nm red shift of the emission maximum and a color change from green to yellow was observed with a slight pH decrease (from 7.0 to 6.8) in the system. This pH-dependent emission could be attributed to the efficient exciton energy transfer from smaller QDs to larger ones, which was controlled by electrostatic-tuned aggregation/disaggregation (low/high pH values) processes of the QDs. In addition to high stability, the emission shift of the QDs was reversible for at least one cycle under optimal conditions. Our pH biosensor may find potential application for monitoring the intracellular pH changes in both physiological and pathological conditions. 相似文献
120.