Cover Picture: Proteomics 16/2008

In this issue of Proteomics you will find the following highlighted articles: Do sugar antennae broadcast ovarian cancer signal? Some enzymes are more or less particular about their substrate or their product e.g. DNA polymerases are less particular than poly(A) polymerase. The same is true of N ‐glycosyltransferases. They accept a variety of nucleotide sugar substrates and can turn out a linear or a branched product depending on conditions. Ovarian cancers are the most fatal of the female genital tract in the western world if not caught before metastasis. If caught early, survival rates are 90% but good screening tests are not available. Abbott et al. explored the patterns of branched bi‐, tri‐, and tetra‐antennary products of up‐regulated glycosyltransferases from human and mouse epithelial ovarian cancer cells. Using qRT‐PCR and lectin blots, they found up‐regulation of FUT8, MGAT1 (human), MGAT2 (mouse), and MGAT5 all of which generate multi‐antennary products, potential biomarkers for ovarian cancer. MGAT4a and ‐4b were also informative. Abbott, K. L. et al., Proteomics 2008, 8 , 3210–3220. Wholesale whole‐cell path scanning for UDP‐GlcNAc dependence UDP N ‐acetylglucosamine (UDPGlcNAc) is a central intermediate in the synthesis and breakdown of a wide variety of polymers in cells so it is no surprise that the level of the metabolite is a sensitive control point for a number of cell pathways. Lau et al. probe the number and names of these pathways by varying the concentration of UDPGlcNAc in cultured cell ­medium. Up‐regulated systems at high concentration included EGF and TGF as well as 128 other genes in 13 functional groups. Up groups covered morphology, metabolism, signaling, transport, transcription, and growth regulation. Down‐regulated paths included p38, Erk, JAK‐STAT, PPAR and Notch. Research tools used included expression arrays and siRNA. Lau, K. S. et al., Proteomics 2008, 8 , 3294–3302. Upside down and backward pays off Sometimes getting a different view of a problem can reveal alternative solutions. Lee et al. , searching for biomarkers for hepatocellular carcinoma, had the problems of adequate resolution, reproducibility and cost per sample when they used conventional quantitative proteomic tools in their search. As an alternative, they examined the qualifications of a two‐dimensional phase fractionation system for peptides. They started by depleting samples of high abundance species and then optionally introducing 18 O by tryptic digestion in 95% H 2 18 O. The first dimension was peptide chromatofocusing followed by a second dimension of nonporous reversed phase chromatography at 50°C. Finally, peptides were sequenced by nano‐LC‐ESI‐MS/MS. When compared to protein 2‐D phase fractionation, the peptide 2‐D phase fractionation was distinctly superior. Comparing plasma samples from normal and HCC patients using the peptide protocol, 13 differentially expressed proteins were observed. Similar high efficiency identification of quantitative differences was observed with tissue samples. Lee, H.‐J. et al., Proteomics 2008, 8 , 3371–3381.