Proteomic Analysis Reveals a Role for RSK in p120-catenin Phosphorylation and Melanoma Cell-Cell Adhesion

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Highlights

• •BioID reveals the proximity partners of RSK family members.
• •All RSK isoforms associate with and phosphorylate p120ctn on Ser320.
• •RSK negatively regulates adherens junctions and reduces cell-cell adhesion.
• •p120ctn phosphorylation plays a role in the reorganization of proximity partners.

     

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.

     

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

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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.

     

Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 as Candidate Therapeutic Target

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Highlights

• •SRPK1 is overexpressed in endometrial cancer and associated with poor survival.
• •SRPK1 promotes endometrial cancer cell growth under nutrient-deprived conditions.
• •Activation of EGFR-IGF1R-AKT signaling promotes resistance to SRPK1 inhibitors.
• •Co-targeting SRPK1 and EGFR-IGF1R synergize blocking endometrial cancer cell growth.

     

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

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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.

     

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

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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.

     

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.

     

The DNA Sensor cGAS is Decorated by Acetylation and Phosphorylation Modifications in the Context of Immune Signaling

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Highlights

• •cGAS acetylations and phosphorylations under basal and immune-stimulated states.
• •K384 and K414 acetylations and S305 phosphorylation inhibit cGAS-mediated apoptosis.
• •Acetylation at K198 stimulates cGAS-dependent interferon signaling.
• •K198 acetylation is decreased upon herpesvirus infection.

     

Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease

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Highlights

• •MS-based clinical assay that accurately determines phospho Rab10 occupancy.
• •Stable isotope labeled phosphopeptide injected as a standard with endogenous tryptic phospho Rab peptide for accurate ratio determination.
• •Determination of pRab levels in neutrophils of Parkinson disease patients.
• •Relevance of pRab levels as marker of PD.

     

ProAlanase is an Effective Alternative to Trypsin for Proteomics Applications and Disulfide Bond Mapping

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Highlights

• •ProAlanase is a powerful protease for efficient low pH disulfide bond mapping.
• •High suitability for analysis of histone family members and their PTMs.
• •Accurate phosphorylation profiling in proline-rich proteins.
• •Sequence coverage increase and full de novo sequencing in combination with trypsin.

     

Glutathionylation Decreases Methyltransferase Activity of PRMT5 and Inhibits Cell Proliferation

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Highlights

• •PRMT5 glutathionylation is increased in aged mice or under oxidative stress.
• •Deglutathionylation of PRMT5 is catalyzed by glutaredoxin-1.
• •PRMT5 glutathionylation decreases its methyltransferase activity.
• •PRMT5 glutathionylation results in G2/M arrest and inhibits cell proliferation.

     

FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family

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Highlights

• •FYN and ABL differentially regulate DCBLD Ser/Thr/Tyr phosphorylation.
• •DCBLD1 and DCBLD2 interactomes are modulated by FYN and ABL.
• •ABL drives a direct DCBLD2/14-3-3 interaction.

     

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.

     

Characterization of Signaling Pathways Associated with Pancreatic β-cell Adaptive Flexibility in Compensation of Obesity-linked Diabetes in db/db Mice

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Highlights

• •db/db β-cells restores appropriate insulin stores and normalize secretory function.
• •Numerous changes in the phosphorylation and sialylation states by euglycemic rest.
• •Restoration of numerous dysfunctional biological processes following euglycemic rest.
• •β-cell adaptive flexibility may lead to improvement in endogenous β-cell function.

     

A Quantitative Tri-fluorescent Yeast Two-hybrid System: From Flow Cytometry to In cellula Affinities

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Highlights

• •Simultaneous quantification of Bait, Prey and Reporter at the single cell level.
• •Two hours of reaction are enough instead of 24–48 h for conventional assays.
• •Potential expression problems of the Bait and Prey can be easily detected.
• •True positive PPIs feature a distinct pattern of Reporter level versus Bait/Prey level.
• •PPIs with unknown affinities can be ranked using an affinity ladder.

     

Sialylation of Asparagine 612 Inhibits Aconitase Activity during Mouse Sperm Capacitation; a Possible Mechanism for the Switch from Oxidative Phosphorylation to Glycolysis

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Highlights

• •During sperm capacitation, 6 proteins become de-silyated, whilst one becomes silyated.
• •Loss of sialylated from Endothelial lipase results in reduction of activity.
• •Silyation of N612 on Aconitase causes loss of activity.
• •Silyation of Aconitase may explain the switch from oxidative phosphorylation to glycolysis during capacitation.

     

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.

     

Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome

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Highlights

• •Urinary proteomes of patients with recurrent UTI, renal scarring, and VUR.
• •80 proteins differentially expressed, compared to healthy controls.
• •62 proteins may be indicative of susceptibility for UTI.
• •Altered acute phase response, extracellular matrix and carbohydrate metabolism.