Dynamic Phosphoproteomics Uncovers Signaling Pathways Modulated by Anti-oncogenic Sphingolipid Analogs

1. Download : Download high-res image (137KB)
2. Download : Download full-size image

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.

     

Integrative Proteomic and Phosphoproteomic Profiling of Testis from Wip1 Phosphatase-Knockout Mice: Insights into Mechanisms of Reduced Fertility*,

1. Download : Download high-res image (105KB)
2. Download : Download full-size image

Highlights

• •Mice lacking Wip1 display spermatogenesis defects at the late-stage germ cell types.
• •Proteome and phosphoproteome profiling reveals impaired dynamics of testis junction.
• •Elevated levels of cytokines may lead to abnormal BTB structure and spermatogenesis.

     

Functional Proteomics and Deep Network Interrogation Reveal a Complex Mechanism of Action of Midostaurin in Lung Cancer Cells

1. Download : Download high-res image (94KB)
2. Download : Download full-size image

Highlights

• •Anticancer activity of midostaurin but not other PKC inhibitors in NSCLC cells.
• •Mechanism of action by network-based integration of chemo- and phosphoproteomics.
• •Midostaurin polypharmacology by simultaneous inhibition of TBK1, PDPK1 and AURKA.
• •Design of synergistic drug combination with PLK1 inhibitor by pathway validation.

     

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

1. Download : Download high-res image (83KB)
2. Download : Download full-size image

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.

     

Effects of Acetylation and Phosphorylation on Subunit Interactions in Three Large Eukaryotic Complexes

1. Download : Download high-res image (66KB)
2. Download : Download full-size image

Highlights

• •Novel PTMs detected in native yeast exosome, RNA polymerase II and proteasome.
• •MD based approach outperforms published tools in predicting PTMs stability effect.
• •Dynamical approach reveals long range effects of PTMs on subunits binding.
• •Acetylations may have a role in local stabilization of protein complex formation.

     

Proteome-wide Analysis of Protein Thermal Stability in the Model Higher Plant Arabidopsis thaliana

1. Download : Download high-res image (128KB)
2. Download : Download full-size image

Highlights

• •Over 1700 Arabidopsis proteins with thermal models in multiple replicates.
• •Melting temperature correlates with 1°, 2°, and 3° protein characteristics.
• •Ligand-induced thermal shifts are evident in complex protein extracts.

     

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

1. Download : Download high-res image (115KB)
2. Download : Download full-size image

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.

     

Proteomic Analysis of Baboon Cerebral Artery Reveals Potential Pathways of Damage by Prenatal Alcohol Exposure,

1. Download : Download high-res image (105KB)
2. Download : Download full-size image

Highlights

• •We studied mid-pregnancy alcohol exposure and baboon fetal cerebral artery.
• •238 proteins differed between control and alcohol-exposed fetuses near-term.
• •Proteins of metabolic pathways represented one of the major targets of alcohol.
• •Alcohol effect on the development of fetal brain vessels is persistent.

     

A Curated Resource for Phosphosite-specific Signature Analysis

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

Highlights

• •Database of PTM site-specific phosphorylation signatures of kinases, perturbations and signaling pathways (PTMsigDB).
• •PTM signature enrichment analysis (PTM-SEA) outperformed gene-centric analysis in detection of EGF induced phospho signaling events.
• •PI3K perturbation signatures were readily detected in PI3Ka inhibited human breast cancer cells.
• •PTMsigDB and PTM-SEA can be freely accessed at https://github.com/broadinstitute/ssGSEA2.0.

     

Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry,

1. Download : Download high-res image (138KB)
2. Download : Download full-size image

Highlights

• •LFQ-based protein patterns define glioma subgroups that correlate with genomic alterations.
• •Proteomic analysis resolves distinct pathway-level differences among glioma subtypes.
• •Distinct IDH subtype-specific tumor patterns are maintained in glioma stem cell cultures.

     

Assembly of the β4-Integrin Interactome Based on Proximal Biotinylation in the Presence and Absence of Heterodimerization,

1. Download : Download high-res image (146KB)
2. Download : Download full-size image

Highlights

• •This study reports the first proteomic characterization of a type II hemidesmosomal complex.
• •This study characterizes the interactome of β4-integrin in the presence and absence of α6-integrin in a simple epithelial cell model.
• •The assembly of the β4-integrin interacting complex was largely independent of α6-integrin expression.

     

Quantitative Mass Spectrometry to Interrogate Proteomic Heterogeneity in Metastatic Lung Adenocarcinoma and Validate a Novel Somatic Mutation CDK12-G879V

1. Download : Download high-res image (203KB)
2. Download : Download full-size image

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.

     

Human Stress-inducible Hsp70 Has a High Propensity to Form ATP-dependent Antiparallel Dimers That Are Differentially Regulated by Cochaperone Binding,

1. Download : Download high-res image (115KB)
2. Download : Download full-size image

Highlights

• •Hsp70 homologs differ in their oligomeric properties in the presence of ATP.
• •Human inducible Hsp70 forms ATP-dependent anti-parallel dimers with high propensity.
• •Dimerization of ATP-bound Hsp70 is required for effective Hsp70-Hsp40 interaction.
• •ATP-dependent interaction with Tomm34 TPR cochaperone disrupts Hsp70 dimer.

     

Temporal Proteomic Analysis of Pancreatic β-Cells in Response to Lipotoxicity and Glucolipotoxicity

1. Download : Download high-res image (133KB)
2. Download : Download full-size image

Highlights

• •Temporal proteome profiling of lipotoxicity and glucolipotoxicity in β-cells
• •Palmitate induced cholesterol metabolism earlier than fatty acid metabolism
• •Setd8 promotes palmitate + glucose-stimulated INS-1 cell proliferation
• •PA induced apoptosis partially via upregulation of Rhob in INS-1 cells

     

Spatial Distribution of Endogenous Tissue Protease Activity in Gastric Carcinoma Mapped by MALDI Mass Spectrometry Imaging

1. Download : Download high-res image (100KB)
2. Download : Download full-size image

Highlights

• •New MALDI MS imaging sample preparation workflow reveals tissue protease activity.
• •Differential time- and inhibitor concentration-dependence confirm active proteases.
• •Mouse gastric tumor displays high protease activity compared to surrounding tissue.
• •Proteomic data and biochemical protease activity assay support MALDI MSI results.

     

Bayesian Confidence Intervals for Multiplexed Proteomics Integrate Ion-statistics with Peptide Quantification Concordance,

1. Download : Download high-res image (74KB)
2. Download : Download full-size image

Highlights

• •Bayesian Beta-Binomial model integrates ion statistics with peptide ratio agreement.
• •Model appropriately interprets information from low signal peptides.
• •Confidence can be assigned even without replicates.
• •Model adds sensitivity to detection of small changes.