Radiosensitization by Kinase Inhibition Revealed by Phosphoproteomic Analysis of Pancreatic Cancer Cells

1. Download : Download high-res image (156KB)
2. Download : Download full-size image

Highlights

• •Proteomes and phosphoproteomes of radiosensitive and radioresistant PDAC cell lines.
• •Common activation of DDR is proven by ATM activity on known and novel substrates.
• •Resistant cells bear raised NQO1 expression, actin dynamics including FAK activity.
• •Inhibitors of CHEK Rabusertib and FAK Defactinib radiosensitize PDAC cells.

     

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

1. Download : Download high-res image (422KB)
2. Download : Download full-size image

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.

     

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

1. Download : Download high-res image (183KB)
2. Download : Download full-size image

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.

     

Combined EGFR and ROCK Inhibition in Triple-negative Breast Cancer Leads to Cell Death Via Impaired Autophagic Flux

1. Download : Download high-res image (244KB)
2. Download : Download full-size image

Highlights

• •We used phosphoproteomics to reveal the underlying mechanisms of drug synergy on EGFR and ROCK co-inhibition in TNBC cells.
• •EGFR inhibition alone induces autophagy activation in TNBC cells as a cytoprotective mechanism.
• •Combinatorial treatment leads to impaired autophagic flux resulting in a strong accumulation of autophagic vacuoles.
• •We hypothesize that ROCKi-induced cytoskeletal changes impair autophagosome clearance ultimately leading to cell death.

     

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

1. Download : Download high-res image (227KB)
2. Download : Download full-size image

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.

     

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

1. Download : Download high-res image (252KB)
2. Download : Download full-size image

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.

     

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

1. Download : Download high-res image (92KB)
2. Download : Download full-size image

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.

     

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

1. Download : Download high-res image (147KB)
2. Download : Download full-size image

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.

     

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

1. Download : Download high-res image (162KB)
2. Download : Download full-size image

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.

     

Molecular Dynamics Simulation-assisted Ionic Liquid Screening for Deep Coverage Proteome Analysis

1. Download : Download high-res image (123KB)
2. Download : Download full-size image

Highlights

• •Mechanistic insights into ionic liquids and proteins at molecular level.
• •Extractants prescreen for proteome analysis with MD simulation system.
• •A loss-less sample preparation method developed for in-depth proteome profiling.
• •Over 3,300 proteins were confidently identified from 1,000 HeLa cells in a 1 h run.
• •Label-free quantitative proteome analysis of human liver cancer tissues.

     

Site-specific N-glycan Analysis of Antibody-binding Fc γ Receptors from Primary Human Monocytes

1. Download : Download high-res image (312KB)
2. Download : Download full-size image

Highlights

• •Monocytes are isolated from single donors after apheresis.
• •Monocytes process CD16a and CD32a N-glycosylation differently by site and donor.
• •CD16a with hybrid and oligomannose type N-glycans bind IgG1 Fc with stronger affinity than complex type.

     

Multi-omic Characterization of the Mode of Action of a Potent New Antimalarial Compound,JPC-3210, Against Plasmodium falciparum

1. Download : Download high-res image (134KB)
2. Download : Download full-size image

Highlights

• •Multi-omics analysis on mode of action of novel antimalarial, JPC-3210
• •JPC-3210 has rapid parasite killing kinetics.
• •Metabolomics and peptidomics demonstrated JPC-3210 inhibits hemoglobin digestion.
• •Proteomics demonstrated JPC-3210 enriches for translation regulation proteins.

     

Molecular Basis of the Mechanisms Controlling MASTL

1. Download : Download high-res image (140KB)
2. Download : Download full-size image

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.

     

Proteome-wide Analysis Reveals Substrates of E3 Ligase RNF146 Targeted for Degradation

1. Download : Download high-res image (134KB)
2. Download : Download full-size image

Highlights

• •Proteome analyses reveal RNF146 and TNKS1/2 substrates targeted for degradation.
• •RNF146 KO and TNKS1/2 DKO cells display significantly different proteomes.
• •RNF146 has both TNKS-dependent and -independent substrates.

     

Phenotypic Adaption of Pseudomonas aeruginosa by Hacking Siderophores Produced by Other Microorganisms

1. Download : Download high-res image (158KB)
2. Download : Download full-size image

Highlights

• •P. aeruginosa grown with exosiderophores and analyzed by proteomic and RT-qPCR.
• •Catechol-type exosiderophores strongly induce the expression of their transporters.
• •Repression of the endogenous iron uptake pathways.
• •Complex phenotypic plasticity in the expression of the various iron-uptake pathways.

     

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

1. Download : Download high-res image (245KB)
2. Download : Download full-size image

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.

     

Novel Proteome Extraction Method Illustrates a Conserved Immunological Signature of MSI-H Colorectal Tumors

1. Download : Download high-res image (249KB)
2. Download : Download full-size image

Highlights

• •TOP: robust, bio-friendly FFPE proteome extraction method with less fixation bias.
• •Proteome of MSI-H colorectal cancer identifies immunobiology key elements.
• •MSI-H tumor displays an “INFg-STAT1 centric signature”.
• •Long-term IFNg induction In-vitro mimicks MSI-H signature.

     

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

1. Download : Download high-res image (209KB)
2. Download : Download full-size image

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.