Sucrose-induced Receptor Kinase 1 is Modulated by an Interacting Kinase with Short Extracellular Domain,

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Highlights

• •Functional role of a yet uncharacterized receptor kinase QSK1.
• •Activation model for SIRK1 receptor kinase in a heteromer with QSK1.
• •Role of QSK1 in substrate recruitment and stabilization of the complex.

     

Global Proteome and Ubiquitinome Changes in the Soluble and Insoluble Fractions of Q175 Huntington Mice Brains

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Highlights

• •Quantitative changes in global proteome and ubiquitinome in Huntington's disease.
• •Differential ubiquitination of wild-type and mutant Htt in mice brain.
• •Enriched pathways include vesicle transport and mRNA processing.
• •Correlation between protein and diGly site fold changes.

     

Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling

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Highlights

• •quantitative phosphoproteome analysis of TDM-activated macrophages.
• •distinct Mincle-dependent and independent phosphorylation and gene regulations.
• •Mincle-dependent activation of PI3K/AKT signaling by TDM.
• •Mincle-independent macrophage response is linked to cell cycle regulation.

     

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.

     

DECA,A Comprehensive,Automatic Post-processing Program for HDX-MS Data*

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Highlights

• •Open source software for comprehensive HDX-MS data analysis.
• •Automatic back-exchange correction options.
• •Rigorous statistical analysis of the significance of uptake differences.
• •High quality visualization tools.

     

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.

     

Salmonella Effectors SseK1 and SseK3 Target Death Domain Proteins in the TNF and TRAIL Signaling Pathways*

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Highlights

• •MS-based method to detect native arginine-GlcNAcylation during Salmonella infection.
• •Demonstration that SseK1 targets TRADD, whereas SseK3 targets the death receptors, TNFR1 and TRAILR.
• •Evidence that effector overexpression results in misleading identification of host targets.
• •Crystal structure of SseK3.

     

Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection of Its Disrupting Antibodies

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Highlights

• •Quantitative co-IP-MS approach to discover the human TEX101 interactome.
• •Validation of the human testis-specific protein complex TEX101-DPEP3.
• •Development of a hybrid immunoassay to screen for disruptors of TEX101-DPEP3 complex.

     

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.

     

Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus

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Highlights

• •C9, GSN, PON1, and PON3 validated as serum biomarker candidates of EAC.
• •Multimarker panel with AUROC of 0.93 to aid current endoscopy surveillance of BE.
• •Induction of tissue C9 in BE, dysplastic BE and EAC.
• •Alteration of complement pathway glycoproteins during BE-EAC pathogenesis.

     

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.

     

Celastrol Protects From Cholestatic Liver Injury Through Modulation of SIRT1-FXR Signaling

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Highlights

• •1. Celastrol alleviated cholestatic liver injury.
• •2. Celastrol inhibited the decrease of SIRT1 induced by deoxycholic acid.
• •3. SIRT1-FXR signaling pathway mediated the effect of celastrol.

     

A New Tool to Reveal Bacterial Signaling Mechanisms in Antibiotic Treatment and Resistance

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Highlights

• •Quantitative (phospho)proteome analysis of antibiotic treatment in E. coli.
• •Largest bacterial phosphorylation catalogue.
• •Specific phosphorylation motifs changes during resistance development.
• •Phosphorylation mediated signaling could be a potential target for drug design.

     

FlashPack: Fast and Simple Preparation of Ultrahigh-performance Capillary Columns for LC-MS*

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Highlights

• •Fast and simple capillary column packing protocol.
• •Low-pressure packing at <100 bars from ultrahigh sorbent suspension concentration.
• •Sorbent particle aggregation leading to blocking of the column entrance is avoided.
• •Effective for long capillary UHPLC column packing with a wide range of sorbents.

     

Proteomic Profiling of Paired Interstitial Fluids Reveals Dysregulated Pathways and Salivary NID1 as a Biomarker of Oral Cavity Squamous Cell Carcinoma,

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Highlights

• •Proteome profiling of tissue interstitial fluids (TIFs) of oral cancer.
• •Pathway of aminoacyl tRNA biosynthesis enriched in proteome of TIFs.
• •Verification of nidogen-1 as a salivary biomarker of oral cancer.
• •High correlation between elevated tissue level of nidogen-1 and poor survival.

     

Sample Preparation Scale-Up for Deep N-glycomic Analysis of Human Serum by Capillary Electrophoresis and CE-ESI-MS*

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Highlights

• •Efficient sample preparation workflow for deep N-glycomics analysis from serum.
• •Temperature gradient denaturing protocol to prevent protein precipitation.
• •Decrease of free sugar content in serum enhanced PNGase F digestion efficiency.
• •Modified evaporative labeling method increased fluorophore labeling yield.

     

MaxQuant.Live Enables Global Targeting of More Than 25,000 Peptides

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Highlights

• •MaxQuant.Live controls Orbitrap mass analyzers in real-time.
• •Freely available apps enable advanced data acquisition strategies.
• •On-the-fly mass, retention time and intensity recalibration.
• •Global targeting unifies shotgun and targeted proteomics.

     

Conodipine-P1-3, the First Phospholipases A2 Characterized from Injected Cone Snail Venom*

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Highlights

• •Three novel Conodipines P1-3 in the injected venom of Conus purpurascens.
• •Conodipines P1-3 have consensus catalytic characteristics of sPLA₂.
• •We determined multiple modification sites in Conodipines P1-3.
• •Evaluated the activity of Conohyal-P1 by a MS-based method.