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71.
Rer1p competes with APH-1 for binding to nicastrin and regulates gamma-secretase complex assembly in the early secretory pathway
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Spasic D Raemaekers T Dillen K Declerck I Baert V Serneels L Füllekrug J Annaert W 《The Journal of cell biology》2007,176(5):629-640
The gamma-secretase complex, consisting of presenilin, nicastrin, presenilin enhancer-2 (PEN-2), and anterior pharynx defective-1 (APH-1) cleaves type I integral membrane proteins like amyloid precursor protein and Notch in a process of regulated intramembrane proteolysis. The regulatory mechanisms governing the multistep assembly of this "proteasome of the membrane" are unknown. We characterize a new interaction partner of nicastrin, the retrieval receptor Rer1p. Rer1p binds preferentially immature nicastrin via polar residues within its transmembrane domain that are also critical for interaction with APH-1. Absence of APH-1 substantially increased binding of nicastrin to Rer1p, demonstrating the competitive nature of these interactions. Moreover, Rer1p expression levels control the formation of gamma-secretase subcomplexes and, concomitantly, total cellular gamma-secretase activity. We identify Rer1p as a novel limiting factor that negatively regulates gamma-secretase complex assembly by competing with APH-1 during active recycling between the endoplasmic reticulum (ER) and Golgi. We conclude that total cellular gamma-secretase activity is restrained by a secondary ER control system that provides a potential therapeutic value. 相似文献
72.
Nesvizhskii AI Roos FF Grossmann J Vogelzang M Eddes JS Gruissem W Baginsky S Aebersold R 《Molecular & cellular proteomics : MCP》2006,5(4):652-670
In mass spectrometry-based proteomics, frequently hundreds of thousands of MS/MS spectra are collected in a single experiment. Of these, a relatively small fraction is confidently assigned to peptide sequences, whereas the majority of the spectra are not further analyzed. Spectra are not assigned to peptides for diverse reasons. These include deficiencies of the scoring schemes implemented in the database search tools, sequence variations (e.g. single nucleotide polymorphisms) or omissions in the database searched, post-translational or chemical modifications of the peptide analyzed, or the observation of sequences that are not anticipated from the genomic sequence (e.g. splice forms, somatic rearrangement, and processed proteins). To increase the amount of information that can be extracted from proteomic MS/MS datasets we developed a robust method that detects high quality spectra within the fraction of spectra unassigned by conventional sequence database searching and computes a quality score for each spectrum. We also demonstrate that iterative search strategies applied to such detected unassigned high quality spectra significantly increase the number of spectra that can be assigned from datasets and that biologically interesting new insights can be gained from existing data. 相似文献
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Roel GW Verhaak Mathijs A Sanders Maarten A Bijl Ruud Delwel Sebastiaan Horsman Michael J Moorhouse Peter J van der Spek Bob Löwenberg Peter JM Valk 《BMC bioinformatics》2006,7(1):337-4
Background
Accurate interpretation of data obtained by unsupervised analysis of large scale expression profiling studies is currently frequently performed by visually combining sample-gene heatmaps and sample characteristics. This method is not optimal for comparing individual samples or groups of samples. Here, we describe an approach to visually integrate the results of unsupervised and supervised cluster analysis using a correlation plot and additional sample metadata. 相似文献74.
J Raemaekers 《Folia primatologica; international journal of primatology》1978,30(3):194-205
Several studies of primates have found that they tend to eat different foods at different times of day. A detailed study of a small sample of siamang and lar gibbons shows that they select figs in the morning, young leaves in the afternoon and figs again for the last feed of the day. Various explanations of these choices are offered, centering on how the gibbons can best meet their energy demands overnight and at dawn. 相似文献
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Keane Jared Guillaume Kenswil Paola Pisterzi Gonzalo Sánchez-Duffhues Claire van Dijk Andrea Lolli Callie Knuth Byambasuren Vanchin Adrian Christopher Jaramillo Remco Michiel Hoogenboezem Mathijs Arnoud Sanders Jacqueline Feyen Tom Cupedo Ivan G. Costa Ronghui Li Eric Moniqué Johannes Bindels Kirsten Lodder Bianca Blom Pieter Koen Bos Marc Hermanus Gerardus Petrus Raaijmakers 《Cell Stem Cell》2021,28(4):653-670.e11
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Ecology of sympatric gibbons 总被引:2,自引:0,他引:2
J Raemaekers 《Folia primatologica; international journal of primatology》1979,31(3):227-245
Ecological compatibility of sympatric gibbons is achieved by a difference in diet resulting from the effect of differing body sizes on the efficiency of harvesting different foods. In addition, differences in feeding apparatus and body size between the large and small species maximise the rate at which each can eat its most eaten food type. Parallels exist between the species array of gibbons and that of the African apes in the relationship between body size and ecology. 相似文献
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Mario Milco DElios Mathijs P. Bergman Amedeo Amedei Ben J. Appelmelk Gianfranco Del Prete 《Microbes and infection / Institut Pasteur》2004,6(15):1395
Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry. 相似文献
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