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BBB seminar: Frauke Melchior

Small ubiquitin-related modifier SUMO-1

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Frauke Melchior
Institute for Biochemistry and Molecular Cell Biology, Dept. of Biochemistry I, Georg August University Göttingen, Germany

Small ubiquitin-related modifier SUMO-1 and its homologs can be reversibly conjugated to a large number of cellular proteins. Since our discovery that SUMOylation of the Ran GTPase-activating protein RanGAP1 is required for it's association with the nuclear pore complex protein RanBP2/Nup358, more than 100 targets for SUMOylation have been identified. Depending on the specific target, SUMOylation serves to regulate protein/protein and protein/DNA interactions as well as intracellular localization and may protect from ubiquitin-dependent degradation. SUMOylation involves an enzymatic cascade that resembles ubiquitination, and the modification can be reverted by isopeptidases. The E1 activating enzyme (Aos1/Uba2) and the E2 conjugating enzyme (Ubc9) are sufficient for modification of some targets in vitro, others require E3 ligases. These include the PIAS (protein inhibitor of activated STAT) protein family, Polycomb protein 2, and RanBP2/Nup358. The properties of RanBP2 distinguish it from all other known E3 ligases, and suggest that it exerts its catalytic effect by altering Ubc9's properties rather than by mediating target interactions.

Selected References:
1) Mahajan, R., Delphin, C., Guan, T., Gerace, L. and Melchior, F. (1997) Cell 88, 97-107
2) Pichler, A., Gast, A., Seeler, J.S., Dejean, A. and Melchior, F. (2002) Cell 108, 109-120
3) Melchior, F. (2000). Annu. Rev. Cell Dev. Biol.,16, 591-626 (review).
4) Pichler, A., Knipscher, P., Saitoh, H., Sixma, T., and Melchior, F. (2004) Nat. Struct. & Mol. Biol. 11, 984 - 991
5) Pichler, A, Knipscheer, P., Oberhofer, E., van Dijk, W.J., Körner, R., Olsen, J.V., Jentsch, S., Melchior, F., and Sixma, T.K. (2005) Nat. Struct. & Mol. Biol. 12, 264-269.

Host: Anni Vedeler, Department of Biomedicine
 

Frauke Melchior is Professor of Biochemistry at the Georg-August University in Göttingen, Germany. She is one of the leading researchers in the field of SUMOylation of proteins and the functional effect of this post-translational modification. SUMOylation is known to play a role in signal transduction, transcription, chromatin remodelling, DNA repair, mitosis, viral infection, and nucleocytoplasmic trafficking. Frauke Melchior has published in high impact journals and in 1998 she received the BioFuture young investigator award of the German Federal Ministry of Education and Research.