Autophagy, the process by which proteins and organelles are sequestered in autophagosomal vesicles and delivered to the lysosome/vacuole for degradation, provides a primary route for turnover of stable and defective cellular proteins. Defects in this system are linked with numerous human diseases. Although conserved protein kinase, lipid kinase and ubiquitin-like protein conjugation subnetworks controlling autophagosome formation and cargo recruitment have been defined, our understanding of the global organization of this system is limited. Here we report a proteomic analysis of the autophagy interaction network in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new autophagy interaction network components have roles in vesicle trafficking, protein or lipid phosphorylation and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The six ATG8 orthologues in humans (MAP1LC3/GABARAP proteins) interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. These studies provide a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.
Pubmed ID: 20562859 RIS Download
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A desktop application for the analysis, visualization and data-mining of large-scale genomic data. It is a versatile microarray tool, incorporating sophisticated algorithms for clustering, visualization, classification, statistical analysis and biological theme discovery. MeV generates informative and interrelated displays of expression and annotation data from single or multiple experiments. A huge array of alrogithms are included in MeV modules, and are available at a button-click, such as K-means clustering, Hierarchical clustering, t-Tests, Significance Analysis of Microarrays, Gene Set Enrichment Analysis, and EASE. Extensive documentation is available for helping new users get started with MeV. A Quickstart Guide provides the tutorial a brand new person will need to get their first dataset loaded and displayed in the program. Returning MEV users will want to check out the release notes to see what new features are available in the latest versions of the program. Tutorials have been written about several of its more involved features.
View all literature mentionsCollection of genome databases for vertebrates and other eukaryotic species with DNA and protein sequence search capabilities. Used to automatically annotate genome, integrate this annotation with other available biological data and make data publicly available via web. Ensembl tools include BLAST, BLAT, BioMart and the Variant Effect Predictor (VEP) for all supported species.
View all literature mentionsSoftware platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsDatabase of known and predicted protein interactions. The interactions include direct (physical) and indirect (functional) associations and are derived from four sources: Genomic Context, High-throughput experiments, (Conserved) Coexpression, and previous knowledge. STRING quantitatively integrates interaction data from these sources for a large number of organisms, and transfers information between these organisms where applicable. The database currently covers 5''214''234 proteins from 1133 organisms. (2013)
View all literature mentionsNon profit research organization for genome sequences to advance understanding of biology of humans and pathogens in order to improve human health globally. Provides data which can be translated for diagnostics, treatments or therapies including over 100 finished genomes, which can be downloaded. Data are publicly available on limited basis, and provided more extensively upon request.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
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