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61.
Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta 总被引:13,自引:0,他引:13
Itoh M Kim CH Palardy G Oda T Jiang YJ Maust D Yeo SY Lorick K Wright GJ Ariza-McNaughton L Weissman AM Lewis J Chandrasekharappa SC Chitnis AB 《Developmental cell》2003,4(1):67-82
Lateral inhibition, mediated by Notch signaling, leads to the selection of cells that are permitted to become neurons within domains defined by proneural gene expression. Reduced lateral inhibition in zebrafish mib mutant embryos permits too many neural progenitors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a RING ubiquitin ligase. Mib interacts with the intracellular domain of Delta to promote its ubiquitylation and internalization. Cell transplantation studies suggest that mib function is essential in the signaling cell for efficient activation of Notch in neighboring cells. These observations support a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell. This facilitates intramembranous cleavage of the remaining Notch receptor, release of the Notch intracellular fragment, and activation of target genes in neighboring cells. 相似文献
62.
Murakami N Ye Y Kawanishi M Aoki S Kudo N Yoshida M Nakayama EE Shioda T Kobayashi M 《Bioorganic & medicinal chemistry letters》2002,12(20):2807-2810
Bioassay-guided separation by use of the fission yeast expressing NES of Rev, a HIV-1 viral regulatory protein, resulted in isolation of valtrate (1) as a new Rev-transport inhibitor from the nucleus to cytoplasm from Valerianae Radix. Valtrate (1) also inhibited the p-24 production of HIV-1 virus without showing any cytotoxicity against the host MT-4 cells. 相似文献
63.
Yuki Doi Motoyuki Shimizu Tomoya Fujita Akira Nakamura Noboru Takizawa Naoki Takaya 《Applied and environmental microbiology》2014,80(6):1910-1918
We identified the extremely nitrite-tolerant bacterium Achromobacter denitrificans YD35 that can grow in complex medium containing 100 mM nitrite (NO2−) under aerobic conditions. Nitrite induced global proteomic changes and upregulated tricarboxylate (TCA) cycle enzymes as well as antioxidant proteins in YD35. Transposon mutagenesis generated NO2−-hypersensitive mutants of YD35 that had mutations at genes for aconitate hydratase and α-ketoglutarate dehydrogenase in the TCA cycle and a pyruvate dehydrogenase (Pdh) E1 component, indicating the importance of TCA cycle metabolism to NO2− tolerance. A mutant in which the pdh gene cluster was disrupted (Δpdh mutant) could not grow in the presence of 100 mM NO2−. Nitrite decreased the cellular NADH/NAD+ ratio and the cellular ATP level. These defects were more severe in the Δpdh mutant, indicating that Pdh contributes to upregulating cellular NADH and ATP and NO2−-tolerant growth. Exogenous acetate, which generates acetyl coenzyme A and then is metabolized by the TCA cycle, compensated for these defects caused by disruption of the pdh gene cluster and those caused by NO2−. These findings demonstrate a link between NO2− tolerance and pyruvate/acetate metabolism through the TCA cycle. The TCA cycle mechanism in YD35 enhances NADH production, and we consider that this contributes to a novel NO2−-tolerating mechanism in this strain. 相似文献
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Based on several previous studies indicating that transfection of genomic DNA can stably alter the character of the cells that take up the exogenous DNA, we investigated antitumor immunity conferred by fusions of syngeneic dendritic cells (DCs) and allogeneic fibroblasts (NIH3T3) transfected with genomic DNA from B16 tumor cells. Fusion cells (FCs) composed of dendritic and genetically engineered NIH3T3 cells were prepared with polyethylene glycol, and fusion efficiency was 30.3%. Prior immunization with FCs prevented tumor formation upon challenge with B16 tumor cells. Efficacy was reduced when studies were performed in mice depleted of NK cells. Vaccination with FCs containing DCs and fibroblasts transfected with denatured DNA did not inhibit tumor growth. Cytotoxic T cell (CTL) activity of spleen cells from immunized mice against both Yac-1 and tumor cells was also stimulated by administration of FCs compared with the activity observed for cells obtained from naïve mice. These data demonstrate the therapeutic efficacy of fusion cell–based vaccine therapy using syngeneic DCs and allogeneic fibroblasts transfected with tumor-derived genomic DNA. 相似文献
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Hiroki Maeda Takeshi Hatta Daigo Tsubokawa Fusako Mikami Toshiyuki Nishimaki Takeshi Nakamura Makoto Matsubayashi Motoyuki Ogawa Clarissa Prazeres da Costa Naotoshi Tsuji 《Parasitology international》2018,67(5):609-611
Parasite-induced behavioral changes in their hosts favor to complete the lifecycle of parasites. Schistosome infection is also known to cause physiological changes in infected freshwater snail intermediate hosts. Here, we report, a novel phenomenon in which Schistosoma mansoni, a highly debilitating worm affecting millions of people worldwide, alters the phototropic behavior of Biomphalaria glabrata, the vector snail. S. mansoni-infection enhanced positive phototropism of vector snails and infected snails spent significantly more time in light. Possibly, these behavioral changes help the parasite to be released efficiently from the infected intermediate hosts, and to infect mammalian hosts. 相似文献
69.
Hitoshi Komatsuzawa Motoyuki Sugai Seiji Nakashima Hidekazu Suginaka 《Microbiology and immunology》1995,39(8):629-633
Profiles of cell-associated bacteriolytic activities and those in the culture supernatant of Staphylococcus aureus FDA209P at various stages of growth were analyzed using sodium dodecyl sulfate-polyacrylamide gels containing Micrococcus luteus or S. aureus. In the logarithmic growth phase, the cell-associated bacteriolytic activities extracted with Triton X-100 contained a number of bacteriolytic proteins, the profiles of which were similar to those we reported elsewhere (Sugai, M., Akiyama, T., Komatsuzawa, H., Miyake, Y., and Suginaka, H.(1990) J. Bacteriol., 172, 6494-6498). The proteins include P1, P2, P7, P9, PX, P13, P18 and other minor components. At the stationary growth phase, the bacteriolytic band-profile of the Triton X-100 extract changed dramatically. P1, P7 and P9 disappeared, and the other minor bands had markedly decreased band intensities. On the other hand, P2, PX, P13, and P18 retained their band intensities during the stationary growth phase. The band intensities of P7, P13, PX, and P18 increased in the supernatant during the logarithmic growth phase. These results indicated that the bacteriolytic band-profile changes during growth. 相似文献
70.
Isao Yokoi Yukiko Namba Hideaki Kabuto Kazunori Inada Motoyuki Iida Akitane Mori Norio Ogawa 《Neurochemical research》1996,21(10):1187-1192
Since nitric oxide (NO) is synthesized by nitric oxide synthase (NOS) froml-arginine (Arg) which has an amidino group in its molecule, we, examined the effect of 29 kinds of Arg analogues on neuronal
NOS (nNOS) activity in the rat brain. None of the Arg analogues acted as a substrate for nNOS. Diamidinocystamine, hirudonine,
and guanethidine inhibited nNOS activity to 67.3%, 64.2% and 74.1%, respectively, but their inhibitory efficiency was lower
than NG-monomethyl-l-arginine (to 36.5%) which is a well known NOS inhibitor. Dimethylguanidine and N-benzoylguanidine also significantly inhibited
nNOS activity to 88.0% and 90.7%, respectively. Whereas almost all of the NOS inhibitors previously reported were synthesizdd
by substituting the amidino nitrogen of Arg, none of these new inhibitors were substituted at this position. Furthermore,
hirudonine, which is a naturally occurring compound, was thought to act as an agonist at polyamine binding site of the N-methyl-d-aspartate type of glutamate receptor complex. It is also interesting that guanethidine, an antihypertensive agent, inhibit
nNOS activity. These new drugs are useful for the investigation not only of the chemical nature of nNOS but also of the physiologic
function of NO. 相似文献