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Article
| Open Access
Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals
Analysis of a large number of Ribo-seq datasets and genomic alignments led to detection of novel non-AUG proteoforms. Unexpectedly the number of non-AUG proteoforms identified with Ribo-seq greatly exceeds those with strong phylogenetic support.
- Alla D. Fedorova
- , Stephen J. Kiniry
- & Pavel V. Baranov
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Article
| Open Access
Stratifin as a novel diagnostic biomarker in serum for diffuse alveolar damage
No reliable serum biomarker for diffuse alveolar damage, a poor prognosis subtype of drug-induced interstitial lung disease, is currently available. Here, the authors show stratifin/14-3-3σ in serum is a promising biomarker for diagnosis of this type of disease.
- Noriaki Arakawa
- , Atsuhito Ushiki
- & Masayuki Hanaoka
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Article
| Open Access
Streamlined single-cell proteomics by an integrated microfluidic chip and data-independent acquisition mass spectrometry
Single-cell proteomics is an emerging approach to characterize cell-to-cell differences. Here, the authors develop chips that enable complete proteomic sample processing down to the single-cell level and integrate them with DIA-MS into a streamlined single-cell proteomics workflow.
- Sofani Tafesse Gebreyesus
- , Asad Ali Siyal
- & Hsiung-Lin Tu
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Article
| Open Access
High-throughput and high-efficiency sample preparation for single-cell proteomics using a nested nanowell chip
Single-cell proteomics is an emerging technology but protein coverage, throughput and quantitation accuracy are often still insufficient. Here, the authors develop a nested nanowell chip that improves protein recovery, throughput and robustness of isobaric labeling-based quantitative single-cell proteomics.
- Jongmin Woo
- , Sarah M. Williams
- & Ying Zhu
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Article
| Open Access
Compensatory ion transport buffers daily protein rhythms to regulate osmotic balance and cellular physiology
Osmotic compensation by electroneutral ion transport buffers TORC1-mediated changes in the cytosolic proteome, and maintains intracellular homeostasis and cell volume over the circadian cycle. Here, the authors find such ion content changes drive daily rhythms in cardiomyocyte electrical activity.
- Alessandra Stangherlin
- , Joseph L. Watson
- & John S. O’Neill
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Article
| Open Access
The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones
Tissue-specific differences in protein folding capacities are poorly understood. Here, the authors show that the human chaperone system consists of ubiquitous core chaperones and tissue-specific variable chaperones, perturbation of which leads to tissue-specific phenotypes.
- Netta Shemesh
- , Juman Jubran
- & Esti Yeger-Lotem
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Article
| Open Access
Protein context shapes the specificity of SH3 domain-mediated interactions in vivo
The SRC Homology 3 (SH3) domains mediate protein–protein interactions (PPIs). Here, the authors assess the SH3-mediated PPIs in yeast, and show that the identity of the protein itself and the position of the SH3 both affect the interaction specificity and thus the PPI-dependent cellular functions.
- Ugo Dionne
- , Émilie Bourgault
- & Christian R. Landry
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Article
| Open Access
Dynamic remodelling of the human host cell proteome and phosphoproteome upon enterovirus infection
Here, Giansanti et al. perform a system-wide and time-resolved characterization of the changes in the host cell proteome and phosphoproteome of cells infected with the enterovirus coxsackievirus B3 during a full round of replication and identify mTORC1 signalling as a major regulation network during virus infection.
- Piero Giansanti
- , Jeroen R. P. M. Strating
- & Frank J. M. van Kuppeveld
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Article
| Open Access
Generating high quality libraries for DIA MS with empirically corrected peptide predictions
Data-independent acquisition-mass spectrometry (MS) typically requires many preparatory MS runs to produce experiment-specific spectral libraries. Here, the authors show that empirical correction of in silico predicted spectral libraries enables efficient generation of high-quality experiment-specific libraries.
- Brian C. Searle
- , Kristian E. Swearingen
- & Mathias Wilhelm
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Article
| Open Access
Genome and epigenome wide studies of neurological protein biomarkers in the Lothian Birth Cohort 1936
Plasma levels of neurological proteins have the potential to serve as biomarkers for neurological conditions. Here, Hillary et al. perform genome- and epigenome-wide association studies for 92 neurological proteins and identify 41 genomic loci for 33 proteins and 26 CpG sites for 9 proteins.
- Robert F. Hillary
- , Daniel L. McCartney
- & Riccardo E. Marioni
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Article
| Open Access
Proteome-wide detection of S-nitrosylation targets and motifs using bioorthogonal cleavable-linker-based enrichment and switch technique
Reversible cysteine modifications play important roles in cellular redox signaling. Here, the authors develop a chemical proteomics strategy that enables the quantitative analysis of endogenous cysteine nitrosylation sites and their dynamic regulation under nitrosative stress conditions.
- Ruzanna Mnatsakanyan
- , Stavroula Markoutsa
- & René P. Zahedi
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Article
| Open Access
WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation
Overexpression of RAS proteins is frequently observed in patients with hepatocellular carcinoma. Here, the authors identify an HRAS binding protein, the E3 ubiquitin ligase WDR76, which promotes HRAS degradation, thus functioning as a tumour suppressor in liver cancer
- Woo-Jeong Jeong
- , Jong-Chan Park
- & Kang-Yell Choi
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Article
| Open Access
Genome‐wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease
Genetic variation can influence levels of disease-related plasma proteins and, thus, contribute to the pathogenesis of complex diseases. Here, the authors perform genome-wide QTL analysis for 71 plasma proteins to identify causal proteins for coronary heart disease and provide a molecular QTL browser.
- Chen Yao
- , George Chen
- & Daniel Levy
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Article
| Open Access
Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator
Although many genetic variants are known for obesity, their function remains largely unknown. Here, in a weight-loss intervention cohort, the authors identify protein quantitative trait loci associated with BMI at baseline and after weight loss and find FAM46A to be a regulator of leptin in adipocytes.
- Jérôme Carayol
- , Christian Chabert
- & Jörg Hager
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Article
| Open Access
Application of bio-orthogonal proteome labeling to cell transplantation and heterochronic parabiosis
Clarifying the source of proteins in mixed biological environments, such as after transplantation or parabiosis, remains a challenge. Here, the authors address this need with a mouse strain that incorporates a methionine derivate into proteins, allowing for their detection using click chemistry and antibody arrays.
- Yan Liu
- , Michael J. Conboy
- & Irina M. Conboy
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Review Article
| Open Access
Accelerating the search for the missing proteins in the human proteome
The Human Proteome Project aims to catalogue the ∼20,000 proteins encoded by the human genome. In this review, Bakeret al. focus on the missing proteins, proteins that lack high stringency proteomic evidence, and launch MissingProteinPedia, a database aimed at accelerating the search for missing proteins.
- Mark S. Baker
- , Seong Beom Ahn
- & Shoba Ranganathan
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Article
| Open Access
Global changes of the RNA-bound proteome during the maternal-to-zygotic transition in Drosophila
Early development is controlled by maternally deposited mRNAs and the RNA-binding proteins (RBPs) that regulate them. Here the authors describe the identification of a large number of RBPs bound to polyadenylated RNAs in Drosophilaembryos before and after the maternal-to-zygotic transition, revealing changes in RBPs activity during development.
- Vasiliy O. Sysoev
- , Bernd Fischer
- & Anne Ephrussi
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Article
| Open Access
Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate
Inflammatory cytokines such as TNF-α influence inflammation, apoptosis and tumour development through regulation of the kinase IKKβ. Krishnan and Nolte et al.apply quantitative proteomics to identify potential IKKβ targets, and reveal phosphorylation of AEG-1 by IKKβ as a mechanism controlling NF-κB signalling.
- Ramesh K. Krishnan
- , Hendrik Nolte
- & Jakub M. Swiercz
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Deep proteome profiling of Trichoplax adhaerens reveals remarkable features at the origin of metazoan multicellularity
Trichoplaxis the most primitive multicellular animal on Earth and thus provides insight into the earliest stages of evolution. Delving deep into the proteome, Heck and colleagues observe a burst in tyrosine phosphorylation, confirming the hypothesis that at the onset of this new communication system a surplus of phosphorylation took place.
- Jeffrey H. Ringrose
- , Henk W.P. van den Toorn
- & Albert J.R. Heck
Automating data analysis for hydrogen/deuterium exchange mass spectrometry using data-independent acquisition methodology