Proteomics articles within Nature Communications

Tumour suppressors are inhibited in cancers and their reactivation could provide novel therapy opportunities. Here, the authors study the structural mechanism by which human tumour suppressor Protein Phosphatase 2A is inhibited in breast cancer cells by the oncoprotein CIP2A.

The failure of metabolic tissues to respond to insulin is an early marker of type 2 diabetes. Here, the authors show, using global phosphoproteomics, that insulin resistance is caused by a marked rewiring of both canonical and non-canonical insulin signalling, and includes dysregulated GSK3 activity.

The 16p11.2 duplication confers risk for autism and schizophrenia, but the disease mechanisms are unknown. Here, the authors use proteomics to show dysregulation of synaptic and epilepsy-associated protein networks in the cortex of model mice, and demonstrate that correcting Prrt2 gene dosage rescues circuit hypersynchrony and behavioural phenotypes.

Integrating genetic information with circulating proteomics can help understand mechanisms of disease. Here, the authors conduct genome-wide association analyses of the serum proteome in 2,958 Han Chinese individuals, uncovering proteins which may contribute to ancestry differences in cardiometabolic disease susceptibility.

Disease-associated mutations in the protein TECPR2 have so far been mainly studied with respect to autophagy. Using complementary proteomics approaches, the authors identify trafficking and sorting defects along the secretory pathway upon TECPR2 deficiency and provide evidence that TECPR2 associates with the ER-Golgi interface.

The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

Influenza A virus replication relies on host cell-derived ubiquitination of the viral polymerase. Here, Günl et al. show that site-specific ubiquitination of PB1-K578 is acquired during infection and facilitates spatiotemporal control of polymerase dimerization and NP binding.

Deubiquitinases (DUBs) are key signaling enzymes, many of which lack selective inhibitors. Chan et al. pair a DUB-focused covalent library to mass spectrometry activity-based protein profiling, leading to selective hits against 23 endogenous DUBs and a first-in-class VCPIP1 probe with nanomolar potency.

Targeted proteomics enables robust hypothesis-driven research. Here, Yu et al. present a multiplexed approach for targeted pathway proteomics and apply it to quantify protein families across 480 fully genotyped Diversity Outbred mice, revealing impacts of genetic variation on protein expression and lipid metabolism.

The proteogenomic landscape of diffuse gliomas remains to be explored. Here, the authors perform proteogenomic characterisation of diffuse gliomas, investigate the functional role of genomic alterations and suggest three proteomic subgroups.

Here the authors establish the SPOC domain as a universal reader of the RNA Pol II CTD code and a versatile reader of phosphoserine marks found in co- and post-transcriptional regulators such as m6A writer and reader proteins.

Many software suites and spectral libraries have been developed for DIA proteomics data analysis. Here, the authors create benchmark data sets to evaluate four commonly used software tools combined with seven spectral libraries in both global proteomics and phosphoproteomics analysis.

Longitudinal proteomics holds great promise for biomarker discovery, but the data interpretation has remained a challenge. Here, the authors evaluate several tools to detect longitudinal differential expression in proteomics data and introduce RolDE, a robust reproducibility optimization approach.

Accurate protein mapping on whole-tissue levels provides critical insights into diseases/therapies. Here, the authors described a novel spatial proteomics method, based on tissue compartmentalization using a 3D-printed micro-scaffold, generated thousands of protein maps across a whole-tissue slice.

Software tools for larger-scale intact glycopeptide quantification lag far behind, which hinders exploring the differential sitespecific glycosylation. Here, the authors report pGlycoQuant, a generic tool with a deep learning model for quantitative glycoproteomics at intact glycopeptide level.

The molecular landscape of microphthalmia transcription factor family translocation renal cell carcinoma tumours remain to be characterised. Here, the authors perform proteogenomic analysis and reveal dysregulation of DNA repair, mTOR signalling and metabolic processes.

Metabolic labeling is often used to measure protein turnover. Here the authors show that for interconvertible protein species like phosphoforms metabolic labeling does not provide information on turnover differences, but that the relative order of modification can determine the observed dynamics.

Spatially resolved proteomics is an emerging approach for mapping proteome heterogeneity. Here, the authors report a method based on the combination of hydrogel-based tissue transformation with mass spectrometry-based proteomics, that enables proteome profiling with a lateral resolution of 160 µm.

Sinonasal tumour diagnosis can be complicated by the heterogeneity of disease and classification systems. Here, the authors use machine learning to classify sinonasal undifferentiated carcinomas into 4 molecular classe with differences in differentiation state and clinical outcome.

Single-cell proteomics is an emerging approach to study cellular heterogeneity but its coverage is still limited. Here, the authors develop a single-cell proteomics approach with improved protein sequence coverage, allowing them to quantify PTMs and characterize effects of inhibitor treatment in single human cells.

Protein phosphorylation is a ubiquitous post-translational modification used to regulate cellular processes and proteome architecture by modulating protein-protein interactions. Here the authors optimize genetically encoded phosphothreonine to study the regulation of CHK2 kinase using large-scale DNA arrays that enable phosphoproteome expression techniques to identify sitespecific overlap between CHK2 substrates and 14-3-3 interactions.

Deep learning (DL) has been frequently used in mass spectrometry-based proteomics but there is still a lot of potential. Here, the authors develop a framework that enables building DL models to predict arbitrary peptide properties with only a few lines of code.

Four T2D subtypes were previously identified: severe insulin deficient, severe insulin resistant, mild obesity-related, and mild age-related diabetes. Here, the authors show that these subtypes can be translated to an Arabic population and identify distinct subtype-specific metabolic and proteomic signatures.

Specificity in signaling activated by receptor tyrosine kinases is typically attributed to characteristics of their intracellular domains. Here, the authors demonstrate that an extracellular receptor sequence motif controls intracellular signaling as a result of extracellular glycan interactions.

The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures.

The characterization of lysine lactylation (Kla) in prokaryotes remains unclear. Here, the authors identify the regulatory enzymes (YiaC as a lactylase and CobB as a delactylase) and functional network of Kla and reveal a Kla-mediated molecular mechanism for glycolysis regulation in Escherichia coli.

Recruitment of Receptor Tyrosine Kinase signalling partners during endocytosis, specifically during recycling to the plasma membrane, is crucial to signal propagation and regulation. Here, the authors reveal FGFR signalling partners proximal to recycling endosomes with a spatially resolved phosphoproteomics approach.

In patients with melanoma, increased RAS/mitogen-activated protein kinase (MAPK) pathway activity is known to drive chemotherapy resistance. Here, the authors identify CDK12 as a downstream effector of the RAS/MAPK pathway and therapeutic target which mediates chemotherapy resistance through increased expression of DNA repair associated genes.

The slit-diaphragm is a cellular junction that is crucial for blood filtration in the kidney. Kocylowski et al. show that the junction-spanning components are embedded in a protein network for dynamic control of filtration; network disturbance leads to severe filtration defects with proteinuria.

Information about O-glycosylation site regulation and occupancy in the human proteome is limited. Here, the authors identify GalNAc transferase-specific glycan sites in human keratinocytes and describe their occupancy.

Protein complexes play a decisive role for lysosomal function. Here, the authors use cross-linking mass spectrometry and integrative modeling to investigate lysosomes and early endosomes; characterizing protein interactions, structures, and the cargo of flotillin-mediated endocytosis.

Bioactive peptides regulate many physiological functions but progress in discovering them has been slow. Here, the authors use a machine learning framework to predict mammalian peptide candidates from the global and local structure of large-scale tissue-specific mass spectrometry data.

Increasing the number of chromosome sets alters the physiology of cells. Here, the authors show that although the number of chromosome sets increases, the proteome does not scale linearly with the increasing ploidy.

Protein abundance is controlled at the transcriptional, translational and posttranslational levels. Here, Öztürk et al. determine proteome changes resulting from individual knockout of 3308 nonessential genes in the yeast S. pombe, infer gene functionality, and show that protein upregulation under stable transcript expression utilizes optimal codons.

Profiling antibody repertoires using proteomic approaches may provide a way of screening for antibody cross-reactivity against SARS-CoV-2 variants. Here the authors use a IgG1 specific cleavage method to analyse the IgG1 repertoire within recovered patients and relate this to antibody binding and neutralisation.

Currently, no approved vaccines for Listeria monocytogenes are available. Here, the authors use immunopeptidomics to map bacterial peptides presented on infected cells and identify antigens that, as mRNA vaccine, provide protection in mice.

The insulin signalling cascade can be inhibited by phosphatases, including Ser/Thr protein phosphatase 2A (PP2A). Here the authors show that Alpha4, a regulator of the PP2A catalytic subunit, modulates insulin receptor tyrosine phosphorylation via the YBX-1/PTP1B pathway and is involved in maintenance of adipose tissue homeostasis and systemic metabolism.

Long-distance regeneration in the adult central nervous system shows severe guidance defects preventing circuit reformation. Here, the authors reveal a comprehensive map of guidance cues in the adult visual system that can be used to modulate the path of regenerating axons to achieve circuit repair.

Changes in protein subcellular localization can be determined using mass spectrometry. Here, the authors present a statistical approach to determine relocalising proteins from spatial proteomics experiments.

Here the authors address how embryos control the timing of specific gene activation in early frog development. They find transcription factors for early gene activation are maternally loaded and remain at constant levels, and rather that order of activation is based on their sequential entry into the nucleus based largely on their respective affinity to importins.

The crucial first step in the biodegradation of polyethylene plastic is oxidation of the polymer. This has traditionally required abiotic pre-treatment, but now Bertocchini and colleagues report two wax worm enzymes capable of catalyzing this oxidation and subsequent degradation at room temperature.

Protein networks have been widely explored but most binding affinities remain unknown, limiting the quantitative interpretation of interactomes. Here the authors measure affinities of 65,000 interactions involving human PDZ domains and target sequence motifs relevant for viral infection and cancer.

Ubiquitin is not only a posttranslational modifier but itself is subject to modifications, such as acetylation. Characterization of distinct acetylated ubiquitin variants reveals that each acetylation site has a particular impact on ubiquitin structure and its protein-protein interaction properties.

Trypanosomes can sense signal molecules and coordinate their movement in response to such signals, a phenomenon termed social motility (SoMo). Here, Bachmaier et al show that cyclic AMP response protein 3 (CARP3) localization to the flagellar tip and its interaction with a number of different adenylate cyclases is essential for migration to tsetse fly salivary glands and for SoMo, therewith linking SoMo and cAMP signaling to trypanosome transmission.

Characterizing the soft protein corona on nanoparticles i.e. the outer layer of the corona, remains a longstanding challenge. Here, the authors develop an in situ method to monitor the dynamic processes of multilayered corona formation and evolution that offers a universal strategy to characterize the soft corona proteome.

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.

Autophagy is known to impact CD4+ T cell proliferation but the identity of autophagosomal components remain unclear. Here the authors leverage a transgenic mouse model to assess the autophagosomal compartment and identify interleukin-7 receptor-α as a key cargo in proliferating CD4+ T cells.

Methods to identify protein interaction networks often suffer from poor spatiotemporal resolution. Here the authors present a light-activated proximity labeling method where the protein of interest is fused to the photosensitizer protein miniSOG, allowing temporally resolved labeling of interactors.

mTORC1 blocks lysosomal nutrient generation. Here, the authors show that mTORC1 inactivation triggers V-ATPase assembly, which rapidly initiates lysosomal acidification and degradation of protein contents throughout the lysosomal population.