Investigating diversity in human plasma proteins

Nedelkov, Dobrin; Kiernan, Urban A.; Niederkofler, Eric E.; Tubbs, Kemmons A.; Nelson, Randall W.

doi:10.1073/pnas.0500426102

Cited by 174 publications

(172 citation statements)

References 29 publications

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“…The present study involves the MS-based characterization of proteomics, bioinformatics and MS-based peak pattern analysis. Characterization of proteomic differences between sets of AML patients with balanced chromosomal translocations is crucial given that any observed variation in its expression pattern and peak pattern may have prognostic and disease relevance (Nedelkov et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Proteomics of acute myeloid leukaemia: cytogenetic risk groups differ specifically in their proteome, interactome and post-translational protein modifications

et al. 2006

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Acute myeloid leukaemia (AML) is characterized by specific cytogenetic aberrations that are strong determinants of prognostic outcome and therapeutic response. Because the pathological outcome of AML patients with cytogenetic abnormalities differs considerably, we hypothesized that their proteome may also differ specifically in their expression pattern, protein interaction pathways and post-translational modifications (PTM). We performed this study using 42 AML patients diagnosed for various cytogenetic abnormalities based on two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MS) and MSMS tandem MS. We could identify significant differences in the proteome and PTM of peptides, later confirmed by other methods, between cytogenetic groups. The interactome analysis based on computational bioinformatics reveals major regulating networks: MAPK8 and MYC for complex aberrant karyotype, TP53 for t(8;21), TP53-MYC-PRKAC for 11q23 and JUN and MYC for Inv(16). Further, we analysed 42 MS spectra representative of hnRNPH1, calreticulin and hnRNPA2/B1 in a peak explorer, which reveals a cytogenetic-specific PTM of b-O-linked N-acetyl glucosamine (O-GlcNAc) of hnRNPH1 in AML patients with 11q23 translocation, an acetylation of calreticulin in t(8;21) translocation and methylation of hnRNPA2/B1 in patients with translocations of t(8;21) and inv(16). This report may lead to a new thinking about AML pathogenesis, as differences at PTM level could be used to distinguish different subtypes of AML.

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Section: Discussionmentioning

confidence: 99%

Proteomics of acute myeloid leukaemia: cytogenetic risk groups differ specifically in their proteome, interactome and post-translational protein modifications

et al. 2006

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“…Nelson et al, 21 it has been applied to study a variety of proteins and peptides, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and has served as the foundation for the nascent field of Population Proteomics. [37][38][39][40][41][42] Roughly, MSIA can be envisioned as ultra high resolution, semiquantitative Western blotting in which protein variants are thoroughly resolved and their molecular masses determined to within less than 2 Da.…”

Section: Methodsmentioning

confidence: 99%

Glycosylation status of vitamin D binding protein in cancer patients

2009

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On the basis of the results of activity studies, previous reports have suggested that vitamin D binding protein (DBP) is significantly or even completely deglycosylated in cancer patients, eliminating the molecular precursor of the immunologically important Gc macrophage activating factor (GcMAF), a glycosidase-derived product of DBP. The purpose of this investigation was to directly determine the relative degree of O-linked trisaccharide glycosylation of serumderived DBP in human breast, colorectal, pancreatic, and prostate cancer patients. Results obtained by electrospray ionization-based mass spectrometric immunoassay showed that there was no significant depletion of DBP trisaccharide glycosylation in the 56 cancer patients examined relative to healthy controls. These results suggest that alternative hypotheses regarding the molecular and/or structural origins of GcMAF must be considered to explain the relative inability of cancer patient serum to activate macrophages.

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“…In addition, there is a large sequence variation among individuals (28). Gel filtration was evaluated for its potential to be a nonperturbing method for studying differential protein binding in such complex fluids and reveals that several plasma proteins are preferentially enriched on the nanoparticles.…”

Section: Gel Filtration Reveals Preferential Binding Of Specific Plasmentioning

confidence: 99%

Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles

Cedervall¹,

Lynch²,

Lindman

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

2,802

2,561

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Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle ''surface,'' leading to a protein ''corona'' that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.

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Investigating diversity in human plasma proteins

Cited by 174 publications

References 29 publications

Proteomics of acute myeloid leukaemia: cytogenetic risk groups differ specifically in their proteome, interactome and post-translational protein modifications

Proteomics of acute myeloid leukaemia: cytogenetic risk groups differ specifically in their proteome, interactome and post-translational protein modifications

Glycosylation status of vitamin D binding protein in cancer patients

Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles

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