August 2021 Issue
- In Brief Liu et al. characterized the proteome of aqueous humor from three types of glaucoma. Fifty-seven primary acute angle-closure glaucoma (PAACG), 50 primary chronic angle-closure glaucoma (PCACG), 35 neovascular glaucoma (NVG), and 33 cataract patient samples were analyzed using data-independent analysis and parallel reaction monitoring. Lipid metabolism, immune response, and cell death pathways showed different degrees of activation among the three types of glaucoma but were all higher relative to cataract. SERPIND1 was discovered as a vital protein in glaucoma.
- In Brief A multi-omics strategy was used to map the proteome, miRNA, metabolome, and lipidome of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Differentially abundant molecules associated with the metastatic phenotype were enriched for key processes and pathways. An integrative analysis revealed 11 ‘hub proteins’ that are correlated with reduced survival and tumor aggressiveness in patients with cancer according to public databases. These EV molecules are candidates as prognostic markers in oral cancer.
- In Brief SARS-CoV-2 nonstructural protein 3 (nsp3) facilitates virion biogenesis and modulates host ubiquitinylation/ISGylation. The SARS-CoV-2 nsp3 host interactome has not been fully characterized. Using affinity purification–mass spectrometry, we identify interactors of SARS-CoV-2 nsp3 and homologs from four CoV strains. We show the N-terminus of SARS-CoV-2 nsp3 interacts with the transcription factor ATF6 and suppresses its stress response. This work examines the interface between a key CoV protein and host cells, highlighting potential dependencies for antiviral therapeutics.
- In Brief Using a quantitative proteomics approach, Li et al. characterized the proteomes of triple-negative breast cancer (TNBC) patient–derived serum exosomes and found the tetraspanin CD151 to be significantly enriched. Proteomic analysis of CD151-deleted exosomes and cells showed regulation of ribosomal and complement protein secretion. CD151-deleted exosomes were shown to significantly decrease the migration and invasion of TNBC cells, indicating that exosomal CD151 may be a potential therapeutic target for TNBC.
- In Brief Candidate HLA class I T-cell epitopes are frequently identified using a single threshold across multiple alleles. However, previous studies have demonstrated that different HLA class I alleles have varying repertoire sizes. In this study, we investigated the performance of different strategies to perform epitope-binding prediction for multiple HLA class I alleles simultaneously. We identified and present here a set of general and allele-specific thresholds that may be used to identify eluted ligands and T-cell epitopes at 80% sensitivity.
- In Brief BRAFV600E is a key oncogenic driver in glioma, melanoma, and colon cancer. These tumors escape mitogen-activated protein kinase pathway inhibition by upregulating mammalian target of rapamycin signaling. Using comprehensive unbiased proteomic and phosphoproteomic analysis of an in vivo BRAFV600E mutant glioma model treated with inhibitors of both these key pathways, we characterize the tumor and stromal response and suggest additional therapeutic targets for BRAF-driven cancers, including epidermal growth factor receptor and class 1 histone deacetylases.
- In Brief Hall et al. profiled the proteome, transcriptome, and metabolome of the aging Drosophila eye. The integrated analysis revealed changes in metabolism, potentially due to decreases in availability of B vitamins, together with chronic activation of immune response.
- In Brief Proximity-dependent biotinylation approaches such as APEX and BioID are used to illuminate cellular organization in cell culture studies but are not often applied to whole organisms. Here, Rosenthal et al. report the development and optimization of a toolkit for proximity-dependent biotinylation with miniTurbo and TurboID in zebrafish embryos. They describe, using the lamin A component of the lamina, protocols and benchmarks for a rapid injection-based strategy that is appropriate for early development and a flexible heat shock inducible transgenic system.