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Subproject 3

Mass spectrometric analysis of the caspase 1-associated secretome

Caspase-1 is an essential regulatory element of pro-inflammatory reactions by its protelytic processing of interleukines IL-1β and IL-18. In addition, caspase-1 is required for Golgi-independent secretion of its substrates. The molecular mechanisms of this secretory pathway still remain unknown.

We will develop an analytical platform to characterize the secretome of cell culture models based on quantitative label-free high-resolution Orbitrap mass spectrometry. The proposed analytical strategy aims to allow a hypophesis-free and independent analysis of samples and controls. The unbiased analytical approach will help to explore and understand the molecular mechanisms underlying the pathway of unconventional secretion in pro-inflammatory processes.

Subproject Manager

Platzhalter Bild

Dr. Andrej Shevchenko

MPI of Molecular Cell Biology and Genetics


Dr. rer. nat. Marc Gentzel
Tel.: 0351-210 2614

Mukesh Kumar
Tel.: 0351-210 2647

Selected Publications

Groessl M, Luksch H, Rösen-Wolff A, Shevchenko A, Gentzel M. Profiling of the human monocytic cell secretome by quantitative label-free mass spectrometry identifies stimulus-specific cytokines and proinflammatory proteins. J Proteomics 2012; 12(18):2833-42.

Vasilj A, Gentzel M, Ueberham E, Gebhardt R, Shevchenko A. Tissue proteomics by one-dimensional gel electrophoresis combined with label-free protein quantification. J Proteome Res 2012; 11,3680-9.

Schuhmann K, Almeida R, Baumert M, Herzog R, Bornstein SR, Shevchenko A. Shotgun lipidomics on a LTQ Orbitrap mass spectrometer by successive switching between acquisition polarity modes. J Mass Spectrom 2012; 47(1):96-104.

Knaust A, Shevchenko A, Shevchenko A. Horizontal carryover of proteins on one-dimensional polyacrylamide gels may jeopardize gel-enhanced liquid chromatography mass spectrometry proteomic interpretations. Anal Biochem 2012; 421(2):779-81.

Danckwardt S, Gantzert AS, Macher-Goeppinger S, Probst HC, Gentzel M, Wilm M, Gröne HJ, Schirmacher P, Hentze MW, Kulozik AE. p38 MAPK controls prothrombin expression by regulated RNA 3' end processing. Mol Cell 2011; 41(3):298-310.

Spirin V, Shpunt A, Seebacher J, Gentzel M, Shevchenko A, Gygi S, Sunyaev S. Assigning spectrum-specific P-values to protein identifications by mass spectrometry. Bioinformatics 2011; 27(8):1128-34.

Edelson-Averbukh M, Shevchenko A, Pipkorn R, Lehmann WD. Discrimination between peptide O-sulfo- and O-phosphotyrosine residues by negative ion mode electrospray tandem mass spectrometry. J Am Soc Mass Spectrom 2011; 22(12):2256-68. 

Krastev DB, Slabicki M, Paszkowski-Rogacz M, Hubner NC, Junqueira M, Shevchenko A, Mann M, Neugebauer KM, Buchholz F. A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly. Nat Cell Biol 2011; 13(7):809-18.

Schuhmann K, Herzog R, Schwudke D, Metelmann-Strupat W, Bornstein SR, Shevchenko A. Bottom-up shotgun lipidomics by higher energy collisional dissociation on LTQ Orbitrap mass spectrometers. Anal Chem 2011; 83(14):5480-7. 

Schwudke D, Schuhmann K, Herzog R, Bornstein SR, Shevchenko A. Shotgun lipidomics on high resolution mass spectrometers. Cold Spring Harb Perspect Biol 2011; 3(9):a004614. doi:10.1101/cshperspect.a004614. (Review)

Herzog R, Schwudke D, Schuhmann K, Sampaio JL, Bornstein SR, Schroeder M, Shevchenko A. A novel informatics concept for high-throughput shotgun lipidomics based on the molecular fragmentation query language. Genome Biol 2011; 12(1):R8. doi:10.1186/gb-2011-12-1-r8.

Feike AC, Rachor K, Gentzel M, Schambony A. Wnt5a/Ror2-induced upregulation of xPAPC requires xShcA. Biochem Biophys Res Commun 2010; 400(4):500-6.

Thoma C, Fraterman S, Gentzel M, Wilm M, Hentze MW. Translation initiation by the c-myc mRNA internal ribosome entry sequence and the poly(A) tail. RNA 2008; 14(8):1579-89.

Kind J, Vaquerizas JM, Gebhardt P, Gentzel M, Luscombe NM, Bertone P, Akhtar A. Genome-wide analysis reveals MOF as a key regulator of dosage compensation and gene expression in Drosophila. Cell 2008; 133(5):813-28.

Danckwardt S, Kaufmann I, Gentzel M, Foerstner KU, Gantzert A, Neu-Yilik G, Bork P, Keller W, Wilm M, Hentze MW, Kulozik AE. Splicing factors stimulate polyadenylation via USEs at non-canonical 3’ end formation signals. EMBO Jour 2007; 26(11):2658-69.

Niggeweg R, Köcher T, Gentzel M, Buscaino A, Taipale M, Akhtar A, Wilm M. A general precursor ion-like scanning mode on quadrupole-TOF instruments compatible with chromatographic separation. Proteomics 2006; 6(1):41-53.

Gentzel M, Köcher T, Ponnusamy S, Wilm M. Preprocessing of tandem mass spectrometric data to support automatic protein identification. Proteomics 2003; 3(8):1597-610.

Kast J, Gentzel M, Wilm M, Richardson K. Noise filtering techniques for electrospray quadrupole time of flight mass spectra. J Am Soc Mass Spectrom 2003; 14(7):766-76.

Walther TC, Askjaer P, Gentzel M, Habermann A, Griffiths G, Wilm M, Mattaj IW, Hetzer M. RanGTP mediates nuclear pore complex assembly. Nature 2003; 7;424(6949):689-94.

Forler D, Kocher T, Rode M, Gentzel M, Izaurralde E, Wilm M. An efficient protein complex purification method for functional proteomics in higher eukaryotes. Nat Biotechnol 2003; 21:89-92.

Makarov EM, Makarova OV, Urlaub H, Gentzel M, Will CL, Wilm M, Lührmann R. Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome. Science 2002; 298(5601):2205-8.

Groessl M,Zava O, Dyson PJ. Cellular uptake and subcellular distribution of ruthenium-based metallodrugs under clinical investigation versus cisplatin. Metallomics 2011; 3:591-599.

Groessl M, Dyson PJ. Bioanalytical and Biophysical Techniques for the Elucidation of the Mode of Action of Metal-Based Drugs. Curr Top Med Chem 2011; 11(21):2632-46.

Groessl M, Fei Z, Dyson PJ, Katsyuba SA, Vikse KL, McIndoe JS. A mass spectrometric and theoretical study of polyiodides: the connection between solid state, solution and gas phases. Inorg Chem 2011; 50(19):9728-3.

Groessl M, Terenghi M, Casini A, Lobinski R, Dyson PJ. Reactivity of anticancer metallodrugs with serum proteins: new insights from size exclusion chromatography-ICP-MS and ESI-MS. J Anal At Spectrom 2010; 25:305-313.

Groessl M, Tsybin YO, Hartinger ChG, Keppler BK, Dyson PJ. Ruthenium versus Platinum: Interactions of Anticancer Metallodrugs with Duplex Oligonucleotides Characterised by Electrospray Ionisation-Mass Spectrometry. J Biol Inorg Chem 2010; 15:677-688.

Groessl M, Bytzek A, Hartinger ChG. The serum protein binding of pharmacologically active gallium(III) compounds assessed by hyphenated CE-MS techniques. Electrophoresis 2009; 30:2720-2727.

Groessl M, Hartinger ChG, Połeć-Pawlak K, Jarosz M, Dyson PJ, Keppler BK. Elucidation of the Interactions of an Anticancer Ruthenium Complex in Clinical Trials with Biomolecules Utilizing Capillary Electrophoresis Hyphenated to Inductively Coupled Plasma-Mass Spectrometry. Chem Biodivers 2008; 5:1609-14.

Groessl M, Hartinger, ChG, Połeć-Pawlak K, Jarosz M, Keppler BK. CE hyphenated to ICP-MS: a Novel Approach for the Analysis of Anticancer Metallodrugs in Human Serum and Plasma. Electrophoresis 2008; 29:2224-2232.

Groessl M, Hartinger ChG, Dyson PJ, Keppler BK. CZE–ICP-MS as a Tool for Studying the Hydrolysis of Ruthenium Anticancer Drug Candidates and Their Reactivity Towards the DNA Model Compound dGMP. Inorg Biochem 2008; 102:1060-1065.

Groessl M, Reisner E, Hartinger ChG, Timerbaev AR, Arion VB, Keppler BK. Structure–Activity Relationships for NAMI-A Type Complexes (HL)[trans-RuCl4L(S-dmso)ruthenate(III)] (L = Imidazole, Indazole, 1,2,4-Triazole,4-Amino-1,2,4-triazole, and 1-Methyl-1,2,4-triazole): Aquation, Redox Properties, Protein Binding, and Antiproliferative Activity. J Med Chem 2007; 50:2185-2193.