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91.
Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels 总被引:2,自引:0,他引:2
Kato M Han TW Xie S Shi K Du X Wu LC Mirzaei H Goldsmith EJ Longgood J Pei J Grishin NV Frantz DE Schneider JW Chen S Li L Sawaya MR Eisenberg D Tycko R McKnight SL 《Cell》2012,149(4):753-767
Eukaryotic cells contain assemblies of RNAs and proteins termed RNA granules. Many proteins within these bodies contain KH or RRM RNA-binding domains as well as low complexity (LC) sequences of unknown function. We discovered that exposure of cell or tissue lysates to a biotinylated isoxazole (b-isox) chemical precipitated hundreds of RNA-binding proteins with significant overlap to the constituents of RNA granules. The LC sequences within these proteins are both necessary and sufficient for b-isox-mediated aggregation, and these domains can undergo a concentration-dependent phase transition to a hydrogel-like state in the absence of the chemical. X-ray diffraction and EM studies revealed the hydrogels to be composed of uniformly polymerized amyloid-like fibers. Unlike pathogenic fibers, the LC sequence-based polymers described here are dynamic and accommodate heterotypic polymerization. These observations offer a framework for understanding the function of LC sequences as well as an organizing principle for cellular structures that are not membrane bound. 相似文献
92.
Yongmei Hu Nan Peng Wenyuan Han Yuxia Mei Zhengjun Chen Xu Feng Yun?Xiang Liang Qunxin She 《Bioscience reports》2012,32(6):609-618
A putative protease gene (tldD) was previously identified from studying tolerance of letD encoding the CcdB toxin of a toxin–antidote system of the F plasmid in Escherichia coli. While this gene is evolutionarily conserved in archaea and bacteria, the proteolytic activity of encoded proteins remained to be demonstrated experimentally. Here we studied Sso0660, an archaeal TldD homologue encoded in Sulfolobus solfataricus by overexpression of the recombinant protein and characterization of the purified enzyme. We found that the enzyme is active in degrading azocasein and FITC–BSA substrates. Protease inhibitor studies showed that EDTA and o-phenanthroline, two well-known metalloprotease inhibitors, either abolished completely or strongly inhibited the enzyme activity, and flame spectrometric analysis showed that a zinc ion is a cofactor of the protease. Furthermore, the protein forms disulfide bond via the Cys416 residue, yielding protein dimer that is the active form of the enzyme. These results establish for the first time that tidD genes encode zinc-containing proteases, classifying them as a family in the metalloprotease class. 相似文献
93.
Xia X Zhang J Zhang Y Wei F Liu X Jia A Liu C Li W She Z Lin Y 《Bioorganic & medicinal chemistry letters》2012,22(8):3017-3019
Three new pimarane diterpenes (1, 2 and 3) as well as a known compound 4, were isolated from the marine-derived fungus HS-1 from Apostichopus japonicus. Their structures and relative stereochemistry of 1-3 were elucidated using a combination of NMR spectroscopy and CD. In the primary bioassay, compounds 1, 2 and 4 inhibited the growth of KB and KBv200 with IC(50) of 3.51, 2.34 μg/mL, 20.74, 14.47 μg/mL, and 3.86, 6.52 μg/mL, respectively. 相似文献
94.
The formation of mRNPs controls the interaction of the translation and degradation machinery with individual mRNAs. The yeast Scd6 protein and its orthologs regulate translation and mRNA degradation in yeast, C.?elegans, D.?melanogaster, and humans by an unknown mechanism. We demonstrate that Scd6 represses translation by binding the eIF4G subunit of eIF4F in a manner dependent on its RGG domain, thereby forming an mRNP repressed for translation initiation. Strikingly, several other RGG domain-containing proteins in yeast copurify with eIF4E/G and we demonstrate that two such proteins, Npl3 and Sbp1, also directly bind eIF4G and repress translation in a manner dependent on their RGG motifs. These observations identify the mechanism of Scd6 function through its RGG motif and indicate that eIF4G plays an important role as a scaffolding protein for the recruitment of translation repressors. 相似文献
95.
B Yang YJ Wu M Zhu SB Fan J Lin K Zhang S Li H Chi YX Li HF Chen SK Luo YH Ding LH Wang Z Hao LY Xiu S Chen K Ye SM He MQ Dong 《Nature methods》2012,9(9):904-906
We have developed pLink, software for data analysis of cross-linked proteins coupled with mass-spectrometry analysis. pLink reliably estimates false discovery rate in cross-link identification and is compatible with multiple homo- or hetero-bifunctional cross-linkers. We validated the program with proteins of known structures, and we further tested it on protein complexes, crude immunoprecipitates and whole-cell lysates. We show that it is a robust tool for protein-structure and protein-protein-interaction studies. 相似文献
96.
本文研究了白芨中的萜类化合物对血管生成的抑制作用.及其抑制血管生成的可能机制。采用萃取和色谱法从白芨中分离和纯化了该萜类化合物。通过鸡胚绒毛囊膜(CAM)和人脐静脉内皮细胞(HUVEC)研究了白芨中萜类化合物及其粗提物对血管及血管内皮细胞的抑制作用。结果表明,含该萜类的粗提物显著抑制鸡胚绒毛尿囊膜血管生成;该萜类纯品能明显抑制HUVEC增殖,且可诱导HUVEC凋亡,包括细胞体积缩小,细胞膜起泡,细胞核裂解,染色质浓缩和边集,出现凋亡小体,DNA降解。因此.白芨萜类化合物的抗血管生成作用与诱导血管内皮细胞凋亡有关。 相似文献
97.
The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown that HBV nucleocapsid protein and the amino-terminal part of polymerase termed as terminal protein (TP) could inhibit interferon signaling. Further, the global gene expression profiles differ in hepatoma cells with and without HBV gene expression and replication. The expression of interferon (IFN) stimulated genes (ISGs) was differently regulated in cells with HBV replication and could be modulated by antiviral treatments. The HBV TP has been found to modulate the ISG expression and enhance the HBV replication. The modulation of the cellular signaling processes by HBV may have significant implications for pathogenesis. 相似文献
98.
She QB Chandarlapaty S Ye Q Lobo J Haskell KM Leander KR DeFeo-Jones D Huber HE Rosen N 《PloS one》2008,3(8):e3065
Background
Dysregulated PI3K/Akt signaling occurs commonly in breast cancers and is due to HER2 amplification, PI3K mutation or PTEN inactivation. The objective of this study was to determine the role of Akt activation in breast cancer as a function of mechanism of activation and whether inhibition of Akt signaling is a feasible approach to therapy.Methodology/Principal Findings
A selective allosteric inhibitor of Akt kinase was used to interrogate a panel of breast cancer cell lines characterized for genetic lesions that activate PI3K/Akt signaling: HER2 amplification or PI3K or PTEN mutations in order to determine the biochemical and biologic consequences of inhibition of this pathway. A variety of molecular techniques and tissue culture and in vivo xenograft models revealed that tumors with mutational activation of Akt signaling were selectively dependent on the pathway. In sensitive cells, pathway inhibition resulted in D-cyclin loss, G1 arrest and induction of apoptosis, whereas cells without pathway activation were unaffected. Most importantly, the drug effectively inhibited Akt kinase and its downstream effectors in vivo and caused complete suppression of the growth of breast cancer xenografts with PI3K mutation or HER2 amplification, including models of the latter selected for resistance to Herceptin. Furthermore, chronic administration of the drug was well-tolerated, causing only transient hyperglycemia without gross toxicity to the host despite the pleiotropic normal functions of Akt.Conclusions/Significance
These data demonstrate that breast cancers with PI3K mutation or HER2 amplification are selectively dependent on Akt signaling, and that effective inhibition of Akt in tumors is feasible and effective in vivo. These findings suggest that direct inhibition of Akt may represent a therapeutic strategy for breast and other cancers that are addicted to the pathway including tumors with resistant to Herceptin. 相似文献99.
应用石蜡切片法、荧光显微镜和紫外分光光度法,对不同年生巴戟天根组织结构的变化进行了观察、对蒽醌类化合物在根中的分布场所及其积累动态进行了研究。结果表明:巴戟天根的结构类似一般多年生草本植物,薄壁细胞是巴戟天根中蒽醌类化合物的分布储存场所,蒽醌类化合物含量随着根生长年限的增加而增加。由以上研究总结出巴戟天以四年或四年以上采收为好,并以根皮厚、木心细者为上品。 相似文献
100.