Profiling the Surfaceome Identifies Therapeutic Targets for Cells with Hyperactive mTORC1 Signaling

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Highlights

• •Quantitative proteomes of the cellular surface changes induced by mTORC1 signaling.
• •Hit validation in human cancer cell lines and biopsies.
• •Functional studies showing new drug targets to which cancer cells with hyperactive mTORC1 may be addicted.
• •A new paradigm for drug development, namely targeting cell surface proteins regulated by mTORC1.

     

Proteomic Analysis Reveals that Topoisomerase 2A is Associated with Defective Sperm Head Morphology

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Highlights

• •Human spermatozoa possess cells of poor morphology that lack nuclear integrity.
• •These cells can be isolated by density separation.
• •Mass spectrometry reveals their nuclei contain excess protein.
• •TOP2A is a promising marker of this poor nuclear development.

     

Glutathionylation Decreases Methyltransferase Activity of PRMT5 and Inhibits Cell Proliferation

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Highlights

• •PRMT5 glutathionylation is increased in aged mice or under oxidative stress.
• •Deglutathionylation of PRMT5 is catalyzed by glutaredoxin-1.
• •PRMT5 glutathionylation decreases its methyltransferase activity.
• •PRMT5 glutathionylation results in G2/M arrest and inhibits cell proliferation.

     

Organellar Maps Through Proteomic Profiling – A Conceptual Guide

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Highlights

• •Organelle profiling maps capture localizations of 1000s of proteins in one experiment.
• •Comparing maps +/− perturbation reveals disease mechanisms & cellular responses.
• •A conceptual guide to planning and interpreting organellar profiling experiments.
• •A cross-study consensus set of human organellar marker proteins.

     

Phosphotyrosine-based Phosphoproteomics for Target Identification and Drug Response Prediction in AML Cell Lines

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Highlights

• •pY phosphoproteomes and dedicated ranking analyses for 16 AML cell lines.
• •RTK drivers, 6 mutant cell lines confirmed, identification for 4 more cell lines.
• •MAPK1/3 phosphorylation for cell lines without TK driver, indicating RAS mutation.
• •Drug target space phosphorylation correlates with drug IC50s in specific cell lines.

     

Molecular Basis of the Mechanisms Controlling MASTL

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Highlights

• •NCMR is crucial for substrate recognition and activity regulation.
• •MASTL conserves a cryptic C-Lobe in the non-conserved middle region.
• •MASTL₄₅₀ containing the cryptic C-lobe is observed in cancer cell lines.
• •Key phosphorylation sites for MASTL provide an activation model.

     

Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis

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Highlights

• •SILAC-based protein quantification of OA hBMSCs undergoing chondrogenesis.
• •Spatially-resolved metabolomics by MSI of hBMSCs in chondrogenic differentiation.
• •Differential metabolic pathways involved in OA compared to control hBMSCs.
• •UDP-glucuronic acid/UDP-GlcNAc synthesis is decreased in chondrogenic OA hBMSCs.

     

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse

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Highlights

• •Sufficient tumor tissues are often unavailable large HLA peptidome discovery.
• •Using patient derived xenograft (PDX) tumors can overcome this limitation.
• •The large PDX HLA peptidomes expand significantly those of the original biopsies.
• •The HLA peptidomes of the PDX tumors included many tumor antigens.

     

Analytical Guidelines for co-fractionation Mass Spectrometry Obtained through Global Profiling of Gold Standard Saccharomyces cerevisiae Protein Complexes

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Highlights

• •Guidelines for studying protein complexes via co-fractionation mass spectrometry.
• •A novel procedure for profiling gold standard protein complexes in CF-MS data.
• •Recommendations for efficient CF-MS fractionation collection.
• •Scoring metric recommendations for precise and sensitive CF-MS data analysis.

     

Global Proteome and Phosphoproteome Characterization of Sepsis-induced Kidney Injury

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Highlights

• •Cecal Ligation Puncture (CLP) mouse model to study sepsis-induced kidney disease.
• •Quantitative global proteome and phosphoproteome profiling of mouse kidneys.
• •Highly significant candidate markers for onset and progression of AKI to CKD.
• •Mechanistic insights into sepsis-associated kidney injuries.

     

Slight Deuterium Enrichment in Water Acts as an Antioxidant: Is Deuterium a Cell Growth Regulator?

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Highlights

• •Deuterium enrichment to 350 ppm accelerates cell proliferation, which is opposite to that of deuterium depletion to 80 ppm.
• •The cell proliferation increases through decreasing ROS amount in mitochondria.
• •Deuterium enriched water acts as an anti-oxidant.
• •Deuterium may be a cell growth regulator in the interval between 80 and 350 ppm.

     

A Novel Mechanism for NF-κB-activation via IκB-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation

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Highlights

• •Liver Mallory-Denk-Body inducers elicited an IκBα-loss and NF-κB-activation.
• •IκBα-loss was due to its sequestration into insoluble cytoplasmic aggregates.
• •Four proteomic approaches identified 10 IκBα-interacting/aggregating proteins.
• •Nup153/RanBP2-aggregation prevented IκBα nuclear entry for ending NF-κB-activation.

     

A Comprehensive Gender-related Secretome of Plasmodium berghei Sexual Stages

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Highlights

• •Quantitative analysis of Plasmodium sexual stage egress secretome.
• •Activated gametocytes release gender-related proteins.
• •Gametocyte egress process involves different types of vesicles.

     

Phosphoproteomic Approaches to Discover Novel Substrates of Mycobacterial Ser/Thr Protein Kinases

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Highlights

• •Mapping kinase-substrate relationships is vital in discovering new tuberculosis drug targets.
• •LC-MS/MS-based phosphoproteomics expand mycobacterial STPK substrate catalogues.
• •We review and integrate MS-generated datasets on novel candidate substrates.
• •Validation studies are necessary to confirm true physiological substrates of STPKs.

     

Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9

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Highlights

• •Acute inhibition of growth-regulatory AGC-kinases Sch9, PKA and Ypk1.
• •Phospho-proteomic profiling of 6373 phsopho-sites.
• •Ypk1 regulates phospho-sites in RRxS/T-context and functionally overlaps with PKA.
• •Ypk1 and PKA activate trehalase activity of Nth1.

     

A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities

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Highlights

• •Simultaneous quantification of Bait, Prey and Reporter at the single cell level.
• •Two hours of reaction are enough instead of 24–48 h for conventional assays.
• •Potential expression problems of the Bait and Prey can be easily detected.
• •True positive PPIs feature a distinct pattern of Reporter level versus Bait/Prey level.
• •PPIs with unknown affinities can be ranked using an affinity ladder.

     

Concentration Determination of >200 Proteins in Dried Blood Spots for Biomarker Discovery and Validation

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Highlights

• •Repeatable quantification of 200 proteins in dried blood spots.
• •Determined lower limit of quantification, repeatability, parallelism and stability.
• •Protein stability in DBS stored at ambient temperatures for up to 2 months.
• •Concentration ranges for 200 proteins in 20 healthy individuals.

     

Genetic Profile and Functional Proteomics of Anal Squamous Cell Carcinoma: Proposal for a Molecular Classification

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Highlights

• •Two molecular groups in anal squamous carcinoma according proteomic profile.
• •Differences in possible targeted processes such as metabolism or immune response.
• •Different percentage of tumor lymphocyte infiltration.
• •Difference in the frequency of ATM variants, related to PPAR inhibitors.