Expansion of the Gene Ontology knowledgebase and resources

Carbon, Seth; Chan, Juancarlos; Kishore, Ranjana; Lee, R.; Müller, Hans‐Michael; Raciti, Daniela; Auken, Kimberley Van; Sternberg, Paul W.

doi:10.1093/nar/gkw1108

Cited by 1,651 publications

(913 citation statements)

References 22 publications

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“…Less obvious is their connection with the second largest cluster (9 nodes), which accounts for proteins involved in oxygen sensing and DNA damage response. Functional enrichment in GO32 terms shows “regulation of transcription from RNA polymerase II promoter in response to hypoxia” (GO:0061418) as the biological process best describing the entire network (count in gene set 10, false discovery rate 4.66 e −18 ). Interactions between pVHL and RNA polymerase II subunits are already known3334.…”

Section: Resultsmentioning

confidence: 99%

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Minervini

Lopreiato

Bortolotto

et al. 2017

Sci Rep

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Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes patients to develop different highly vascularized cancers. pVHL targets the hypoxia-inducible transcription factor (HIF-1α) for degradation, modulating the activation of various genes involved in hypoxia response. Hypoxia plays a relevant role in regulating cell cycle progression, inducing growth arrest in cells exposed to prolonged oxygen deprivation. However, the exact molecular details driving this transition are far from understood. Here, we present novel interactions between pVHL and the cyclin-dependent kinase inhibitor family CDKN1 (p21, p27 and p57). Bioinformatics analysis, yeast two-hybrid screening and co-immunoprecipitation assays were used to predict, dissect and validate the interactions. We found that the CDKN1 proteins share a conserved region mimicking the HIF-1α motif responsible for pVHL binding. Intriguingly, a p27 site-specific mutation associated to cancer is shown to modulate this novel interaction. Our findings suggest a new connection between the pathways regulating hypoxia and cell cycle progression.

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Section: Resultsmentioning

confidence: 99%

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Minervini

Lopreiato

Bortolotto

et al. 2017

Sci Rep

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“…Protein abundance was determined according to the intensity-based absolute quantification (iBAQ) metric [23]. Gene ontology was investigated with FunRich v3.1.3 using the Gene Ontology Database [24,25]. The peptides identified by mass spectrometry were visualised using Protter [26] with membrane orientations as specified in UniProt annotations [27].…”

Section: Methodsmentioning

confidence: 99%

Enrichment of extracellular vesicles from human synovial fluid using size exclusion chromatography

Foers

Chatfield

Dagley

et al. 2018

J of Extracellular Vesicle

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As a complex biological fluid, human synovial fluid (SF) presents challenges for extracellular vesicle (EV) enrichment using standard methods. In this study of human SF, a size exclusion chromatography (SEC)-based method of EV enrichment is shown to deplete contaminants that remain after standard ultracentrifugation-based enrichment methods. Specifically, considerable levels of serum albumin, the high-density lipoprotein marker, apolipoprotein A-I, fibronectin and other extracellular proteins and debris are present in EVs prepared by differential ultracentrifugation. While the addition of a sucrose density gradient purification step improved purification quality, some contamination remained. In contrast, using a SEC-based approach, SF EVs were efficiently separated from serum albumin, apolipoprotein A-I and additional contaminating proteins that co-purified with high-speed centrifugation. Finally, using high-resolution mass spectrometry analysis, we found that residual contaminants which remain after SEC, such as fibronectin and other extracellular proteins, can be successfully depleted by proteinase K. Taken together, our results highlight the limitations of ultracentrifugation-based methods of EV isolation from complex biological fluids and suggest that SEC can be used to obtain higher purity EV samples. In this way, SEC-based methods are likely to be useful for identifying EV-enriched components and improving understanding of EV function in disease.

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“…MGI's Gene Ontology project provides functional annotations for mouse gene products using the gene ontology (Ashburner et al, 2000;Gene Ontology Consortium, 2017). …”

Section: Mouse Genome Informatics (Mgi)mentioning

confidence: 99%

Invited review: Genetic and genomic mouse models for livestock research

2018

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Abstract. Knowledge about the function and functioning of single or multiple interacting genes is of the utmost significance for understanding the organism as a whole and for accurate livestock improvement through genomic selection. This includes, but is not limited to, understanding the ontogenetic and environmentally driven regulation of gene action contributing to simple and complex traits. Genetically modified mice, in which the functions of single genes are annotated; mice with reduced genetic complexity; and simplified structured populations are tools to gain fundamental knowledge of inheritance patterns and whole system genetics and genomics. In this review, we briefly describe existing mouse resources and discuss their value for fundamental and applied research in livestock.

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Expansion of the Gene Ontology knowledgebase and resources

Cited by 1,651 publications

References 22 publications

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors

Enrichment of extracellular vesicles from human synovial fluid using size exclusion chromatography

Invited review: Genetic and genomic mouse models for livestock research

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