Research in our group centers around posttranslational modification with small ubiquitin-related proteins of the SUMO family. Like ubiquitin, these proteins can be covalently and reversibly linked to other proteins. Attachment of SUMO serves to regulate protein-protein interactions, subcellular localization, enzymatic activity and stability.
Projects in the lab aim at understanding mechanisms, regulation and function of SUMOylation in mammalian cells. We are interested in basic principles of reversible sumoylation (enzymes, targets and acceptor sites), connections between SUMOylation and nucleocytoplasmic transport (focusing, e.g., on the nucleoporin and E3 Ligase RanBP2/Nup358), links between SUMO- and ubiquitin-conjugation pathways, and regulation of sumoylation by redox-signaling
Stankovic-Valentin N, Drzewicka K, König C, Schiebel E, Melchior F (2016). Redox regulation of SUMO enzymes isrequired for ATM activity and survival in oxidative stress. EMBO J, 2016 Jun 15:35(12):1312-29.
Ritterhoff, T., Das, H., Hofhaus, G., Schröder, R.R., Flotho, A., and Melchior, F. (2016). The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependant nuclear export complexes. Nat Commun 7, 11482
Becker, J., Barysch, S.V., Karaca, S., Dittner, C., Hsiao, H.H., Berriel Diaz, M., Herzig, S., Urlaub, S.,Melchior, F. (2013). Detecting endogenous SUMO targets in mammalian cells and tissues. Nat. Struct. Mol. Biol 20(4):525-531.
Werner, A., Disanza, A., Reifenberger, N., Habeck, G., Becker, J., Calabrese, M., Urlaub, H., Lorenz, H., Schulman, B., Scita, G., Melchior F. (2013). SCF(Fbxw5) mediates transient degradation of actin remodeller Eps8 to allow proper mitotic progression. Nat Cell Biol. 15(2):179-88.
Werner, A., Flotho, A., Melchior, F. (2012). The RanBP2/RanGAP1*SUMO1/Ubc9 Complex Is a Multisubunit SUMO E3 Ligase. Mol Cell. 46, 287-298.
Meulmeester, E., Kunze, M., Hsiaoh, H.H., Urlaub, H., Melchior, F. (2008). Mechanism and consequences of paralog specific sumoylation of USP25. Mol Cell 30, 610-619.
Bossis, G. and Melchior, F. (2006). Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes. Mol. Cell 21, 349-357.
Pichler, A., Gast, A., Seeler, J.S., Dejean, A. and Melchior, F. (2002). The nucleoporin RanBP2 is a SUMO1 E3 Ligase. Cell 108, 109-120
Mahajan, R., Delphin, C., Guan, T., Gerace, L. and Melchior, F. (1997). A small ubiquitin related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88, 97-107
Flotho, A and Melchior, F. (2013). Sumoylation: a regulatory protein modification in health and disease. Annu Rev Biochem 82, 357-85. (Article)
Meulmeester, E. and Melchior, F. (2008). Cell Biology: SUMO. Nature 452, 709-711.
Geiss-Friedlander, R. and Melchior F. (2007). Concepts in SUMOylation: a decade on. Nat. Rev. Mol. Cell Biol. 8, 947-956
Barysch, S.V., Dittner, C., Flotho, A., Becker, J., Melchior, F. (2014). Identification and analysis of endogenous SUMO1 and SUMO2/3 targets in mammalian cells and tissues using monoclonal antibodies.Nat. Protoc. 2014 Apr;9(4):896-909.
Stankovic-Valentin, N., Kozaczkiewicz, L., Curth, K. and Melchior, F. (2009). An in vitro FRET-based assay for the analysis of SUMO conjugation and isopeptidase cleavage. Methods in Molecular Biology: SUMO Protocols (Editor H. D. Ulrich): 497: 241-251.
Werner, A., Moutty, M.C., Moeller, U. and Melchior, F. (2009). Performing in vitro sumoylation reactions using recombinant enzymes. Methods in Molecular Biology: SUMO Protocols (Editor H. D. Ulrich): 497: 187-199.