Post-translational modifications and their biological functions: proteomic analysis and systematic approaches.

Recently produced information on post-translational modifications makes it possible to interpret their biological regulation with new insights. Various protein modifications finely tune the cellular functions of each protein. Understanding the relationship between post-translational modifications and functional changes ("post-translatomics") is another enormous project, not unlike the human genome project. Proteomics, combined with separation technology and mass spectrometry, makes it possible to dissect and characterize the individual parts of post-translational modifications and provide a systemic analysis. Systemic analysis of post-translational modifications in various signaling pathways has been applied to illustrate the kinetics of modifications. Availability will advance new technologies that improve sensitivity and peptide coverage. The progress of "post-translatomics", novel analytical technologies that are rapidly emerging, offer a great potential for determining the details of the modification sites.

[1]  E. Nordhoff,et al.  Sample purification and preparation technique based on nano-scale reversed-phase columns for the sensitive analysis of complex peptide mixtures by matrix-assisted laser desorption/ionization mass spectrometry. , 1999, Journal of mass spectrometry : JMS.

[2]  M. Mann,et al.  Proteomic analysis of post-translational modifications , 2003, Nature Biotechnology.

[3]  Tony Pawson,et al.  Regulation and targets of receptor tyrosine kinases. , 2002, European journal of cancer.

[4]  Glycoprotein detection of 2-D separated proteins. , 1999, Methods in molecular biology.

[5]  H. Yano,et al.  Disulfide proteome in the analysis of protein function and structure , 2002, Proteomics.

[6]  D. Hochstrasser,et al.  Method for identification and quantitative analysis of protein lysine methylation using matrix‐assisted laser desorption/ionization — time‐of‐flight mass spectrometry and amino acid analysis , 1999, Electrophoresis.

[7]  G. Hart,et al.  Proteomic approaches to analyze the dynamic relationships between nucleocytoplasmic protein glycosylation and phosphorylation. , 2003, Circulation research.

[8]  M. Görlach,et al.  Functional proteomics analysis of signal transduction pathways of the platelet-derived growth factor beta receptor. , 1999, Biochemistry.

[9]  P. Dupree,et al.  Glycosylphosphatidylinositol‐anchored cell‐surface proteins from Arabidopsis , 1999, Electrophoresis.

[10]  P. Righetti,et al.  Formulations for immobilized pH gradients including pH extremes , 1989, Electrophoresis.

[11]  R. Dwek,et al.  Sequencing of N-linked oligosaccharides directly from protein gels: in-gel deglycosylation followed by matrix-assisted laser desorption/ionization mass spectrometry and normal-phase high-performance liquid chromatography. , 1997, Analytical biochemistry.

[12]  A. Burlingame,et al.  Characterization of protein glycosylation by mass spectrometry. , 1996, Current opinion in biotechnology.

[13]  J. Baenziger,et al.  A Major Step on the Road to Understanding a Unique Posttranslational Modification and Its Role in a Genetic Disease , 2003, Cell.

[14]  P. Ghezzi,et al.  Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Robert Tjian,et al.  Regulating the Regulators Lysine Modifications Make Their Mark , 2003, Cell.

[16]  Kap-Seok Yang,et al.  Reversing the Inactivation of Peroxiredoxins Caused by Cysteine Sulfinic Acid Formation , 2003, Science.

[17]  E. Sheta,et al.  Proteomic Analysis of S-Nitrosylated Proteins in Mesangial Cells * , 2003, Molecular & Cellular Proteomics.

[18]  P. Roepstorff,et al.  Characterization of purified recombinant Bet v 1 with authentic N-terminus, cloned in fusion with maltose-binding protein. , 1996, Protein expression and purification.

[19]  David C Schwartz,et al.  A superfamily of protein tags: ubiquitin, SUMO and related modifiers. , 2003, Trends in biochemical sciences.

[20]  P. Cirri,et al.  Redox regulation of protein tyrosine phosphatases during receptor tyrosine kinase signal transduction. , 2003, Trends in biochemical sciences.

[21]  Steven P Gygi,et al.  A proteomics approach to understanding protein ubiquitination , 2003, Nature Biotechnology.

[22]  Miles Congreve,et al.  Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B , 2003, Nature.

[23]  Tony Kouzarides,et al.  Acetylation: a regulatory modification to rival phosphorylation? , 2000, The EMBO journal.

[24]  N. Packer,et al.  Analyzing glycoproteins separated by two‐dimensional gel electrophoresis , 1998, Electrophoresis.

[25]  M. Mann,et al.  18O-labeling of N-glycosylation sites to improve the identification of gel-separated glycoproteins using peptide mass mapping and database searching. , 1999, Analytical chemistry.

[26]  R. Deschenes,et al.  New insights into the mechanisms of protein palmitoylation. , 2003, Biochemistry.

[27]  G. Georgiou.  How to Flip the (Redox) Switch , 2002, Cell.

[28]  S. Gygi,et al.  Electrophoresis combined with novel mass spectrometry techniques: Powerful tools for the analysis of proteins and proteomes , 1998, Electrophoresis.

[29]  E. J. Song,et al.  Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. , 2002, Cell.

[30]  M. Mann,et al.  4. Proteomic Analysis of Posttranslational Modifications , 2013 .

[31]  V. Lee,et al.  Are Ubiquitination Pathways Central to Parkinson's Disease? , 2003, Cell.

[32]  S. Carr,et al.  Phosphopeptide analysis by matrix-assisted laser desorption time-of-flight mass spectrometry. , 1996, Analytical chemistry.

[33]  M. Mann,et al.  Mapping of phosphorylation sites of gel-isolated proteins by nanoelectrospray tandem mass spectrometry: potentials and limitations. , 1999, Analytical chemistry.

[34]  J. H. Schwartz.  Ubiquitination, Protein Turnover, and Long-Term Synaptic Plasticity , 2003, Science's STKE.

[35]  A. Dejean,et al.  Nuclear and unclear functions of SUMO , 2003, Nature Reviews Molecular Cell Biology.

[36]  Jin Young Kim,et al.  Probing lysine acetylation with a modification-specific marker ion using high-performance liquid chromatography/electrospray-mass spectrometry with collision-induced dissociation. , 2002, Analytical chemistry.

[37]  Kristin A. Hogquist,et al.  Sweet 'n' sour: the impact of differential glycosylation on T cell responses , 2002, Nature Immunology.

[38]  P. Roepstorff,et al.  Mass spectrometric characterization of glycosylated interferon‐γ variants separated by gel electrophoresis , 1996, Electrophoresis.

[39]  P. Schultz,et al.  Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Peter Roepstorff,et al.  Electrospray ionization and matrix assisted laser desorption/ionization mass spectrometry: Powerful analytical tools in recombinant protein chemistry , 1996, Nature Biotechnology.

[41]  B. Kuster,et al.  Perspectives in the glycosciences – matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of carbohydrates , 1998, Glycoconjugate Journal.

[42]  Kong-Joo Lee,et al.  Proteomic Analysis of Protein Phosphorylations in Heat Shock Response and Thermotolerance* , 2002, The Journal of Biological Chemistry.

[43]  G. Hart,et al.  O-GlcNAc: a regulatory post-translational modification. , 2003, Biochemical and biophysical research communications.

[44]  M. Kussmann,et al.  Matrix-assisted laser desorption/ionization mass spectrometric peptide mapping of the neural cell adhesion protein neurolin purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis or acidic precipitation. , 1997, Journal of mass spectrometry : JMS.

[45]  A. Stensballe,et al.  Characterization of phosphoproteins from electrophoretic gels by nanoscale Fe(III) affinity chromatography with off‐line mass spectrometry analysis , 2001, Proteomics.

[46]  S. Carr,et al.  Selective detection and sequencing of phosphopeptides at the femtomole level by mass spectrometry. , 1996, Analytical biochemistry.

[47]  B. Freeman,et al.  NO-dependent protein nitration: a cell signaling event or an oxidative inflammatory response? , 2003, Trends in biochemical sciences.

[48]  Moon-Kyoung Bae,et al.  Regulation and Destabilization of HIF-1α by ARD1-Mediated Acetylation , 2002, Cell.