| 1. |
- Cepeda, D., et al.
(författare)
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CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer
- 2013
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018
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Tidskriftsartikel (refereegranskat)abstract
- SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
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| 2. |
- Fagerberg, Linn, et al.
(författare)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 3. |
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| 4. |
- Fagerberg, Linn, et al.
(författare)
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Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
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Tidskriftsartikel (refereegranskat)abstract
- A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
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| 5. |
- Nair, Arjun, et al.
(författare)
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Variable radiological lung nodule evaluation leads to divergent management recommendations
- 2018
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:6, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Radiological evaluation of incidentally detected lung nodules on computed tomography (CT) influences management. We assessed international radiological variation in 1) pulmonary nodule characterisation; 2) hypothetical guideline-derived management; and 3) radiologists' management recommendations.107 radiologists from 25 countries evaluated 69 CT-detected nodules, recording: 1) first-choice composition (solid, part-solid or ground-glass, with percentage confidence); 2) morphological features; 3) dimensions; 4) recommended management; and 5) decision-influencing factors. We modelled hypothetical management decisions on the 2005 and updated 2017 Fleischner Society, and both liberal and parsimonious interpretations of the British Thoracic Society 2015 guidelines.Overall agreement for first-choice nodule composition was good (Fleiss' κ=0.65), but poorest for part-solid nodules (weighted κ 0.62, interquartile range 0.50-0.71). Morphological variables, including spiculation (κ=0.35), showed poor-to-moderate agreement (κ=0.23-0.53). Variation in diameter was greatest at key thresholds (5 mm and 6 mm). Agreement for radiologists' recommendations was poor (κ=0.30); 21% disagreed with the majority. Although agreement within the four guideline-modelled management strategies was good (κ=0.63-0.73), 5-10% of radiologists would disagree with majority decisions if they applied guidelines strictly.Agreement was lowest for part-solid nodules, while significant measurement variation exists at important size thresholds. These variations resulted in generally good agreement for guideline-modelled management, but poor agreement for radiologists' actual recommendations.
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