Surface Loops in a Single SH2 Domain Are Capable of Encoding the Spectrum of Specificity of the SH2 Family,

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Highlights

• •Surface loops play an essential role in SH2 domain specificity.
• •Diverse specificities may be obtained from a single SH2 domain by combinatorial mutations in the EF and BG loops.
• •The specificity of a loop mutant correlates with the sequence characteristics of the bait peptide used in its isolation.

     

Quantitative Early Auxin Root Proteomics Identifies GAUT10, a Galacturonosyltransferase,as a Novel Regulator of Root Meristem Maintenance

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Highlights

• •Auxin responsive proteins in Arabidopsis roots were identified from 3,514 detected proteins.
• •All six auxin receptors are stable in response to hormone via novel MRM assays.
• •The >100 differentially expressed proteins exhibit dynamic and transient responses to auxin.
• •Phenotypic screening of the top responsive proteins uncovered several novel root mutants.

     

Metabolic,Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*

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Highlights

• •In-depth proteome profiling of primary human myeloma cells
• •Characteristics of myeloma cells are related to hypoxic bone marrow conditions
• •Myeloma cells show specific immune evasion strategies
• •Metabolic adaptations involve tumor and stroma cells

     

Quantitative Mass Spectrometry to Interrogate Proteomic Heterogeneity in Metastatic Lung Adenocarcinoma and Validate a Novel Somatic Mutation CDK12-G879V

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Highlights

• •Serial biopsies and autopsy from a metastatic lung cancer patient over 7 years.
• •Tumor heterogeneity characterized by quantifying the proteome and phosphoproteome.
• •Patient-specific database built using whole genome sequencing data from tumors.
• •MRM assay and functional validation of a novel lung-specific CDK12-G879V mutant.

     

Functional Proteomics and Deep Network Interrogation Reveal a Complex Mechanism of Action of Midostaurin in Lung Cancer Cells

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Highlights

• •Anticancer activity of midostaurin but not other PKC inhibitors in NSCLC cells.
• •Mechanism of action by network-based integration of chemo- and phosphoproteomics.
• •Midostaurin polypharmacology by simultaneous inhibition of TBK1, PDPK1 and AURKA.
• •Design of synergistic drug combination with PLK1 inhibitor by pathway validation.

     

Integration and Analysis of CPTAC Proteomics Data in the Context of Cancer Genomics in the cBioPortal

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Highlights

• •Support for mass spectrometry-based proteomics in cBioPortal.
• •User-friendly web interface, a web API, and an R client to query proteogenomic data.
• •Integration of Clinical Proteomics Tumor Analysis Consortium data with cBioPortal.

     

Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry,

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Highlights

• •LFQ-based protein patterns define glioma subgroups that correlate with genomic alterations.
• •Proteomic analysis resolves distinct pathway-level differences among glioma subtypes.
• •Distinct IDH subtype-specific tumor patterns are maintained in glioma stem cell cultures.

     

microRNA-222 Attenuates Mitochondrial Dysfunction During Transmissible Gastroenteritis Virus Infection

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Highlights

• •microRNA-222 attenuates TGEV-induced mitochondrial dysfunction.
• •microRNA-222 downregulates THBS1 and CD47.
• •THBS1 is the target of microRNA-222 during TGEV infection.
• •THBS1 and CD47 increase mitochondrial Ca²⁺ level and reduced mitochondrial membrane potential (MMP).

     

Complexome Profiling Reveals Association of PPR Proteins with Ribosomes in the Mitochondria of Plants

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Highlights

• •Plant mitoribosomes contain several pentatricopeptide repeat proteins.
• •The small mitoribosomal subunit is of an exceptionally large size.
• •Protein units not directly related to translation may be attached to plant mitoribosomes to confer additional functions to these molecular machines.

     

Quantitative Proteomics of the Mitotic Chromosome Scaffold Reveals the Association of BAZ1B with Chromosomal Axes,

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Highlights

• •Quantitative proteomics of mitotic chromosome scaffold isolated from chicken DT40 cells.
• •BAZ1B identified in the isolated mitotic chromosome scaffold localizes to mitotic chromosome axes.
• •BAZ1B knockout caused prophase delay because of altered chromosome condensation timing and impaired mitosis progression.
• •BAZ1B knockout did not affect prometaphase chromosome structure.

     

Identification of a Specific Translational Machinery via TCTP–EF1A2 Interaction Regulating NF1-associated Tumor Growth by Affinity Purification and Data-independent Mass Spectrometry Acquisition (AP-DIA),

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Highlights

• •AP-DIA/SWATH analysis to identify TCTP-interacting proteins in NF1 tumor cells.
• •A highly specific TCTP–EF1A2 interaction but rather than TCTP–EF1A1 interaction.
• •TCTP–EF1A2 interaction mediating formation of EF1A2-elogation factor complex.
• •TCTP–EF1A2 dependent translation machinery regulating NF1 tumor cell growth.

     

Spatial Distribution of Endogenous Tissue Protease Activity in Gastric Carcinoma Mapped by MALDI Mass Spectrometry Imaging

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Highlights

• •New MALDI MS imaging sample preparation workflow reveals tissue protease activity.
• •Differential time- and inhibitor concentration-dependence confirm active proteases.
• •Mouse gastric tumor displays high protease activity compared to surrounding tissue.
• •Proteomic data and biochemical protease activity assay support MALDI MSI results.

     

Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs

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Highlights

• •Quantitative phosphoproteomics of cells treated with sphingolipid analogs or PP2A inhibitor identify novel protein targets of PP2A.
• •PP2A substrates include several nutrient transporter proteins, GTPase regulators and proteins associated with actin cytoskeletal remodeling.
• •Differential regulation of Akt and Gsk3b account for the difference in vacuolating phenotype observed between SH-BC-893 and C2-ceramide.
• •Dynamic phosphoproteomics enabled the correlation of cell signaling with phenotypes to rationalize their mode of action.

     

Identification of Salivary Biomarkers for Oral Cancer Detection with Untargeted and Targeted Quantitative Proteomics Approaches

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Highlights

• •iTRAQ-based analysis of saliva samples from oral cancer patients.
• •Proteome profiling of saliva samples from patients with oral premalignant lesions.
• •Verification of salivary biomarker candidates with MRM-MS and immunoassays.
• •Identification of salivary proteins as potential biomarkers of oral cancer.

     

Mass Spectrometry-based Absolute Quantification of 20S Proteasome Status for Controlled Ex-vivo Expansion of Human Adipose-derived Mesenchymal Stromal/Stem Cells

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Highlights

• •Design of an MRM assay to determine the absolute quantity and stoichiometry of ubiquitous and tissue-specific human 20S proteasome subtypes.
• •Use of purified isotopically labelled 20S proteasome as internal standard for accurate quantification.
• •Variation in the expression of immunoproteasome in adipocyte-derived stem cells (ADSCs) grown under different O₂ levels might be causal for change in cells differentiation capacity.
• •The status of 20S proteasome during ADSCs expansion might constitute an additional relevant quality control parameter to contribute to predict, among other quality markers, their therapeutic capacity.

     

NOTCH Activation Promotes Valve Formation by Regulating the Endocardial Secretome

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Highlights

• •MEEC are a reliable endocardial in vitro model.
• •Quantitative proteomics to characterize the NOTCH-driven endocardial secretome.
• •NOTCH pathway status underlies different paracrine biological functions.
• •New insights into secreted factors involved in cardiac valve development.