SETD1A Methyltransferase Is Physically and Functionally Linked to the DNA Damage Repair Protein RAD18

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Highlights

• •Protein interaction screen of SETD1A/COMPASS complex subunits.
• •Unexpected interaction with DNA damage protein RAD18 was confirmed for SETD1A, but not for other subunits.
• •SETD1A and/or RAD18 influence each other's mRNA and protein expression levels, and disruption of either gene elicits a similar DNA damage sensitivity phenotype.

     

Phytoplasma-induced Changes in the Acetylome and Succinylome of Paulownia tomentosa Provide Evidence for Involvement of Acetylated Proteins in Witches' Broom Disease

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Highlights

• •Quantitative global proteome, acetylome and succinylome of phytoplasma-infected Paulownia tomentosa seedlings.
• •Acetylation may be more important than succinylation in response to phytoplasma infection.
• •Acetylation modified the activities of POR and RuBisCO.
• •Possible model to elucidate the molecular mechanism responses to PaWB from proteome and PTMs.

     

A Combined N-terminomics and Shotgun Proteomics Approach to Investigate the Responses of Human Cells to Rapamycin and Zinc at the Mitochondrial Level

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Highlights

• •Rapamycin and zinc induce moderate but significant mitochondrial proteome changes.
• •The mitochondrial proteins processing system is robust under subtoxic conditions.
• •Rapamycin and zinc perturb the mitochondrial proteins processing system.
• •Rapamycin and zinc perturb the mitochondrial proteins homeostasis.

     

Spatiotemporal Changes of the Phagosomal Proteome in Dendritic Cells in Response to LPS Stimulation*

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Highlights

• •Characterization of the phagosomal proteome comparing resting and LPS-treated BMDCs.
• •Label-free quantification determined 2843 phagosomal proteins.
• •Reduced recruitment of hydrolases and V-ATPase to phagosomes of LPS-treated cells.
• •Increased recruitment of antigen cross-presentation molecules to these phagosomes.

     

Glycoproteogenomics: A Frequent Gene Polymorphism Affects the Glycosylation Pattern of the Human Serum Fetuin/α-2-HS-Glycoprotein

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Highlights

• •Frequent genetic polymorphism affects the glycosylation pattern of fetuin.
• •Personalized in-depth proteoform profiling of fetuin purified from 20 donors.
• •Classification of serum donors into three different genotypes.
• •Septic patients show increased level of fucosylation at N-glycolation site N176.

     

Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts

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Highlights

• •Changes to the proteome of skin fibroblasts subjected to reductive stress have been quantitated.
• •Only a small set of proteins is selectively diminished upon exposure to reductants.
• •Collagens (COL1A2 and COL6A2) emerge as sentinels of reductive stress.
• •Reductive stress triggers receptor-independent Akt phosphorylation at Ser473.

     

Regulated Phosphosignaling Associated with Breast Cancer Subtypes and Druggability,

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Highlights

• •Our search identifies 2,134 kinase-substrate phosphosite pairs in breast cancer.
• •CDKs and MAPKs are dominant regulators of trans substrate-phosphorylation.
• •Druggability, outcomes, and immune signatures related to kinase-substrates.
• •Experimentally validated activated phosphosites of ERBB2, EIF4EBP1, and EGFR.

     

Comprehensive Analysis of Individual Variation in the Urinary Proteome Revealed Significant Gender Differences

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Highlights

• •Comprehensive analysis of inter-individual variation of normal urinary proteome.
• •Significant gender differences were observed.
• •Proteins increased in female urine are enriched in immunological pathways.
• •Estimated reference intervals of proteins as the baseline for biomarker discovery.

     

Posttranslational Modifications Drive Protein Stability to Control the Dynamic Beer Brewing Proteome

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Highlights

• •SWATH-MS profiles protein abundance and modification during mashing in beer brewing.
• •Proteolysis due to barley proteases leads to extreme proteoform diversity.
• •Sequence-specific proteolytic clipping of proteins controls their stability.

     

In-depth Proteome of the Hypopharyngeal Glands of Honeybee Workers Reveals Highly Activated Protein and Energy Metabolism in Priming the Secretion of Royal Jelly

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Highlights

• •In-depth proteome underpins the gland ontogeny and age-specific activity of the HGs.
• •The well-developed acini in the HGs of NBs promote the RJ secretary activities.
• •The enhanced protein and energy metabolism in the HGs boost the stronger RJ secretion of RJBs.

     

Intact Transition Epitope Mapping – Targeted High-Energy Rupture of Extracted Epitopes (ITEM-THREE),

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Highlights

• •Multiplex epitope mapping/antigenic determinant identification in the gas phase.
• •Intact transition and controlled dissociation of immune complexes by MS.
• •Simultaneous identification and amino acid sequence determination of epitopes.
• •Simplified in-solution sample handling because of ion manipulation and filtering by MS.

     

Identification of Novel Protein Targets of Dimethyl Fumarate Modification in Neurons and Astrocytes Reveals Actions Independent of Nrf2 Stabilization

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Highlights

• •Dimethyl fumarate covalently modifies cysteine residues in neurons and astrocytes.
• •Cofilin-1, tubulin and collapsin response mediator protein 2 (CRMP2) are targets.
• •DMF-modified cofilin-1 reduces actin-severing ability, preserving filamentous actin.

     

Insulin Induces Microtubule Stabilization and Regulates the Microtubule Plus-end Tracking Protein Network in Adipocytes

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Highlights

• •Insulin Affects the Phosphorylation of G2L1, MARK2, CLIP2, EB1, AGAP3, and CKAP5.
• •Insulin Increases CLASP2 +TIP Density and Decreases CLASP2 +TIP Velocity.
• •Insulin Stimulates CLASP2 and G2L1 Trailing Along Microtubules.
• •Insulin Stimulates α-Tubulin Acetylation at Lysine 40 and Microtubule Stabilization.

     

Quantitative Microproteomics Based Characterization of the Central and Peripheral Nervous System of a Mouse Model of Krabbe Disease

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Highlights

• •Quantitative microproteomics to study the CNS and PNS of the Twitcher mouse.
• •10plex TMT experiments on corpus callosum, motor cortex and sciatic nerves extracts.
• •More than 400 proteins groups deregulated between Twitcher and wildtype mice.
• •New insights into the molecular mechanisms of Krabbe disease.

     

Quantitative Multiplex Substrate Profiling of Peptidases by Mass Spectrometry

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Highlights

• •Quantitative substrate profiling method for characterizing peptidase specificity.
• •Applicable to both purified peptidases and peptidases in complex biological samples.
• •TMT labeling improves throughput, accuracy and reproducibility of the assay.
• •Design of fluorescent probes to monitor peptidase activity based on substrate data.

     

Small-protein Enrichment Assay Enables the Rapid,Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma

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Highlights

• •Development of a method for low-abundance small protein analysis in human plasma.
• •Deep proteome profiling demonstrated unbiased identification of diverse factors.
• •Method enabled identification of a novel human plasma protein C5ORF46.
• •Analysis of intermittent fasting response showed changes in iron regulation.

     

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.