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Yuna Sugimoto Michiko Murohashi Satoko Arakawa Shinya Honda Shigeomi Shimizu 《Biochemical and biophysical research communications》2019,508(2):480-486
In chemical biology, the elucidation of chemical target is crucial for successful drug development. Because MHC class I molecules present peptides from intracellular damaged proteins, it might be possible to identify targets of a chemical by analyzing peptide sequences on MHC class I. Therefore, we treated cells with the autophagy-inducing chemical TMD-457 and identified the peptides presented on MHC class I. Many of the peptides were derived from molecules involved in ER trafficking and ER stress, which were confirmed by morphological and biochemical analyses. Therefore, our results demonstrate that analyzing MHC class I peptides is useful for the detection of chemical targets. 相似文献
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The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development
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Gotoh N Manova K Tanaka S Murohashi M Hadari Y Lee A Hamada Y Hiroe T Ito M Kurihara T Nakazato H Shibuya M Lax I Lacy E Schlessinger J 《Molecular and cellular biology》2005,25(10):4105-4116
The docking protein FRS2alpha is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2alpha in vivo remains unknown. In this report, we show that Frs2alpha-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic day 8. We demonstrate that FRS2alpha is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2alpha also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2alpha-null embryos. These experiments underscore the critical role of FRS2alpha in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis. 相似文献
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Akari Fukuda Hiroki Hagiwara Toyoho Ishimura Mariko Kouduka Seiichiro Ioka Yuki Amano Urumu Tsunogai Yohey Suzuki Takashi Mizuno 《Microbial ecology》2010,60(1):214-225
Although deep subterranean crystalline rocks are known to harbor microbial ecosystems, geochemical factors that constrain
the biomass, diversity, and metabolic activities of microorganisms remain to be clearly defined. To better understand the
geochemical and microbiological relationships, we characterized granitic groundwater collected from a 1,148- to 1,169-m-deep
borehole interval at the Mizunami Underground Research Laboratory site, Japan, in 2005 and 2008. Geochemical analyses of the
groundwater samples indicated that major electron acceptors, such as NO3− and SO42−, were not abundant, while dissolved organic carbon (not including organic acids), CH4 and H2, was moderately rich in the groundwater sample collected in 2008. The total number of acridine orange-stained cells in groundwater
samples collected in 2005 and 2008 were 1.1 × 104 and 5.2 × 104 cells/mL, respectively. In 2005 and 2008, the most common phylotypes determined by 16S rRNA gene sequence analysis were both
related to Thauera spp., the cultivated members of which can utilize minor electron donors, such as aromatic and aliphatic hydrocarbons. After
a 3–5-week incubation period with potential electron donors (organic acids or CH4 + H2) and with/without electron acceptors (O2 or NO3−), dominant microbial populations shifted to Brevundimonas spp. These geomicrobiological results suggest that deep granitic groundwater has been stably colonized by Thauera spp. probably owing to the limitation of O2, NO3−, and organic acids. 相似文献