ORCID Profile
0000-0002-1098-3878
Current Organisations
University of Manchester
,
The University of Manchester Faculty of Biology Medicine and Health
,
University of Surrey
,
Bloodwise
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Publisher: Elsevier BV
Date: 03-2008
Publisher: Cold Spring Harbor Laboratory
Date: 22-06-2019
DOI: 10.1101/679845
Abstract: Spectral matching sequence database search engines commonly used on mass spectrometry-based proteomics experiments excel at identifying peptide sequence ions, and in addition, possible sequence ions carrying post-translational modifications (PTMs), but most do not provide confidence metrics for the exact localization of those PTMs when several possible sites are available. Localization is absolutely required for downstream molecular cell biology analysis of PTM function in vitro and in vivo. Therefore, we developed PTMProphet, a free and open-source software tool integrated into the Trans-Proteomic Pipeline, which reanalyzes identified spectra from any search engine for which pepXML output is available to provide localization confidence to enable appropriate further characterization of biologic events. Localization of any type of mass modification (e.g., phosphorylation) is supported. PTMProphet applies Bayesian mixture models to compute probabilities for each site eptide spectrum match where a PTM has been identified. These probabilities can be combined to compute a global false localization rate at any threshold to guide downstream analysis. We describe the PTMProphet tool, its underlying algorithms and demonstrate its performance on ground-truth synthetic peptide reference datasets, one previously published small dataset, one new larger dataset, and also on a previously published phospho-enriched dataset where the correct sites of modification are unknown. Data have been deposited to ProteomeXchange with identifier PXD013210.
Publisher: Elsevier BV
Date: 11-2013
Publisher: Springer Science and Business Media LLC
Date: 06-2016
DOI: 10.1038/NATURE18288
Publisher: Public Library of Science (PLoS)
Date: 28-01-2011
Publisher: Springer Science and Business Media LLC
Date: 21-09-2017
DOI: 10.1038/S41598-017-09722-Z
Abstract: The glucocorticoid receptor (GR) is essential for the stress response in mammals. We investigated potential non-transcriptional roles of GR in cellular stress response using fission yeast as a model.We surprisingly discovered marked heat stress resistance in yeast ectopically expressing human GR, which required expression of both the N-terminal transactivation domain, and the C-terminal ligand binding domain, but not the DNA-binding domain of the GR. This effect was not affected by GR ligand exposure, and occurred without significant GR nuclear accumulation. Mechanistically, the GR survival effect required Hsp104, and, indeed, GR expression increased Hsp104 expression. Proteomic analysis revealed GR binding to translasome components, including eIF3, a known partner for Sty1, a pattern of protein interaction which we confirmed using yeast two-hybrid studies.Taken together, we find evidence for a novel pathway conferring stress resistance in yeast that can be activated by the human GR, acting by protein-protein mechanisms in the cytoplasm. This suggests that in organisms where GR is natively expressed, GR likely contributes to stress responses through non-transcriptional mechanisms in addition to its well-established transcriptional responses.
Publisher: Proceedings of the National Academy of Sciences
Date: 06-04-2015
Abstract: We have discovered a role for the glucocorticoid receptor (GR) in coordinating cell ision. We find enrichment of GR to mitotic spindles and demonstrate that GR knockdown causes accumulation of mitotic defects, including delayed anaphase, ternary chromosome segregation, and death in mitosis. Mitotic GR function requires the ligand-binding domain but not ligand binding, revealing a nontranscriptional and ligand-independent mechanism of action. Analysis of GR haploinsufficient cells and tissues reveals increased aneuploidy and DNA damage, and mice show an increased incidence of tumors in vivo, with further GR loss within those incident tumors. We also identify reduced GR expression in several common human cancers, thereby implicating GR as a novel tumor suppressor gene.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for ANTHONY D WHETTON.