The Challenge of Classifying Metastatic Cell Properties by Molecular Profiling Exemplified with Cutaneous Melanoma Cells and Their Cerebral Metastasis from Patient Derived Mouse Xenografts

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Highlights

• •Comprehensive molecular profiling of cutaneous and cerebellar metastasis variants.
• •Identification of differentially regulated metastasis-associated molecules.
• •Evidence for individually distinct patterns of metastasis-associated molecules.
• •Highlighting the evident need for establishing meta-analyses strategies.

     

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.

     

Characterization of Prenylated C-terminal Peptides Using a Thiopropyl-based Capture Technique and LC-MS/MS

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Highlights

• •Brain membrane protein extraction.
• •Protein prenylation.
• •Prenyl peptide capture and characterization by LC-MS/MS.
• •HCD and EThcD peptide fragmentation.

     

A Cross-linking Mass Spectrometry Approach Defines Protein Interactions in Yeast Mitochondria

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Highlights

• •XL-MS reveals new PPIs in yeast mitochondria under glycerol and glucose condition.
• •Significant but limited results from quantitative XL-MS experiments.
• •Ndi1 participates in a CIII₂CIV₂ respiratory supercomplex.
• •Min8 promotes assembly of Cox12 into an intermediate complex IV.

     

Immediate Adaptation Analysis Implicates BCL6 as an EGFR-TKI Combination Therapy Target in NSCLC

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Highlights

• •EGFR-TKI molecular response profiling covering 10138 proteins and 13486 mRNAs.
• •EGFR-TKI combination therapy screen using a library of 528 compounds.
• •Several new candidate EGFR-TKI escape mechanisms and combination therapy targets.
• •Combined targeting of the oncogene BCL6 and EGFR results in synergy in NSCLC cells.

     

Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane

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Highlights

• •Identification of subcellular protein interactomes via proximity labeling and quantitative multiplexed proteomics.
• •SEC61β and RPN1 interactomes overlap with translocon-associated protein networks.
• •SEC62 interacts with redox-linked proteins and ER luminal chaperones.
• •LRRC59 directly interacts with mRNA translation factors and SRP machinery on the ER.

     

The Insulin Receptor Adaptor IRS2 is an APC/C Substrate That Promotes Cell Cycle Protein Expression and a Robust Spindle Assembly Checkpoint

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Highlights

• •Chemical proteomics in G₁ cells treated with small molecule APC/C inhibitors reveals novel putative APC/C substrates.
• •The insulin receptor adaptor IRS2 is an APC/C substrate that is targeted for degradation by APC/C^Cdh1.
• •Quantitative proteomics in IRS2 knockout cells reveals a deficiency in cell cycle related protein expression.
• •IRS2 promotes a robust spindle assembly checkpoint (SAC) during M-phase.

     

Fast Quantitative Analysis of timsTOF PASEF Data with MSFragger and IonQuant

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Highlights

• •MSFragger now supports raw timsTOF PASEF data.
• •IonQuant performs fast and accurate feature detection and quantification.
• •MSFragger and IonQuant provide excellent performance for timsTOF PASEF data.
• •Flexibility allows for complex analyses, such as semi-enzymatic and open search.

     

Depolarization-dependent Induction of Site-specific Changes in Sialylation on N-linked Glycoproteins in Rat Nerve Terminals

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Highlights

• •Comprehensive sialiomics of isolated rat synaptosomes.
• •Site-specific modulation of sialic acids on surface glycoproteins after brief depolarization.
• •Sialylation as dynamic modification important for synaptic depolarization-dependent processes.

     

An Interaction Network of RNA-Binding Proteins Involved in Drosophila Oogenesis

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Highlights

• •Label-free and dimethyl labeling MS analysis of 6 RBPs from Drosophila ovaries.
• •Functionally related RBPs show overlapping proteomes.
• •Selective co-purification of splicing factors and translational regulators.
• •Validation of 26 novel interactions by co-immunoprecipitation.

     

An Improved Boosting to Amplify Signal with Isobaric Labeling (iBASIL) Strategy for Precise Quantitative Single-cell Proteomics

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Highlights

• •Higher AGC significantly improves quantitation quality in single-cell analysis.
• •The boosting-to-sample ratio should be carefully evaluated and optimized.
• •iBASIL allows for precise quantitation of 1,500 proteins from 104 AML single cells.
• •iBASIL recapitulates major biological differences in different AML single cells.

     

Quantitative Proteomics of Human Heart Samples Collected In Vivo Reveal the Remodeled Protein Landscape of Dilated Left Atrium Without Atrial Fibrillation

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Highlights

• •Proteomes measured from human heart biopsies collected in-vivo covers >7000 cardiac proteins and highlight hundreds of chamber-specific molecular signatures that meaningfully reflect the specialized functions of the respective chambers.
• •Protein quantification from freshly collected biopsies is preferential to necropsy samples because of unspecific post-mortem protein degradation in the latter.
• •Increased abundances of proteins associated with sustained atrial fibrillation are not a sufficient condition to generate the disease state.
• •Protein abundance differences between atria and ventricle primarily originate at the level of gene regulation and reflect a functional need.

     

The Capture of a Disabled Proteasome Identifies Erg25 as a Substrate for Endoplasmic Reticulum Associated Degradation

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Highlights

• •Epitope-tagging of a proteasome subunit allows for facile immuno-isolation.
• •An engineered yeast strain permits capture of proteasome-associated substrates.
• •MS/MS identified all 33 resident proteasome subunits in the 20S and 19S particles.
• •Analysis of associated proteins and characterization of newly identified ERAD substrate.

     

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.

     

Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome

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Highlights

• •Detection of low-abundance phosphotyrosine-containing peptides is challenging.
• •Multiplexed TMT allows inclusion of modification(pTyr)-saturated boost channels.
• •Boost channels facilitate selection of pTyr precursor ions for fragmentation.
• •Quantitation depth is increased while maintaining accuracy and precision.

     

Asparagine Hydroxylation is a Reversible Post-translational Modification

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Highlights

• •Quantitative mass spectrometric method to monitor PTM stability.
• •Pulse labeling reveals dehydroxylation of several asparagine hydroxylation sites.
• •Reversal of TNKS2, TRPV3 and HIF1a asparagine hydroxylation sites.
• •Protein dehydroxylation is an additional level of control for cellular signaling networks.

     

Integration of IgA and IgG Autoantigens Improves Performance of Biomarker Panels for Early Diagnosis of Lung Cancer

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Highlights

• •HuProt array-based identification of autoantigens in serum of early lung cancer.
• •Independent validation of early lung cancer biomarker candidates with ELISA.
• •Bioinformatics-aided identification of a biomarker panel.
• •Independent verification of the panel with ELISA and immunohistochemistry.

     

Robust Summarization and Inference in Proteome-wide Label-free Quantification

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Highlights

• •In depth performance assessment of leading tools for differential protein abundance.
• •Novel fast modular framework MSqRobSum for robust protein summarization and inference.
• •MsqRobSum outperforms leading protein summarization-based tools.
• •MSqRobSum is on par with top-performing peptide based tool MSqRob.

     

Benefits of Collisional Cross Section Assisted Precursor Selection (caps-PASEF) for Cross-linking Mass Spectrometry

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Highlights

• •Cross-linked peptides are physically separated from mono-linked peptides in the gas-phase by TIMS ion mobility.
• •Development of a novel data acquisition routine that a-priori distinguishes cross-linked from mono-linked peptides called caps-PASEF.
• •First application of PhoX-driven cross-linking mass spectrometry on the timsTOF Pro.
• •Application of cross-linking mass spectrometry to medium to high complexity samples.