|
Research in our group centerd 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 aimed at understanding mechanisms, regulation and function of SUMOylation in mammalian cells. We studied basic principles of reversible sumoylation (enzymes, targets and acceptor sites), connections between SUMOylation and nucleocytoplasmic transport, links between SUMO- and ubiquitin-conjugation pathways, and regulation of sumoylation by redox-signaling.
For an introduction into the world of SUMO, see:
https://www.youtube.com/watch?v=X2AxZu05U4U
Selected publications
Reviews
Stankovic-Valentin, N. and Melchior, F. (2018). Control of SUMO and Ubiquitin by ROS: Signaling and disease implications. Mol Aspects Med. 2018, Epub ahead of print. Review.
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
Melchior, F. (2000). SUMO-1-Non-Classical Ubiquitin. Annu. Rev. Cell Dev. Biol., 16, 591-626. (Abstract)
Original Papers
Alfaro AJ, Dittner C, Becker J, Loft A, Mhamane A, Maida A, Georgiadi A, Tsokanos FF, Klepac K, Molocea CE, El-Merahbi R, Motzler K, Geppert J, Karikari RA, Szendrödi J, Feuchtinger A, Hofmann S, Karaca S, Urlaub H, Berriel Diaz M, Melchior F, Herzig S. Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism. EMBO Rep. 2023 Aug 10:e55981. doi: 10.15252/embr.202255981. Epub ahead of print. PMID: 37560809.
Schweiggert J, Habeck G, Hess S, Mikus F, Beloshistov R, Meese K, Shoji H, Knobeloch KP, Melchior F (2021). SCFFbxw5 targets kinesin-13 proteins to facilitate ciliogenesis. EMBO J, 2021;e107735.
Barysch S V, N, Stankovic-Valentin N, Miedema T, Karaca S, Doppel J, Nait Achour T, Vasudeva A, Wolf L, Sticht C, Urlaub H, Melchior F (2021). Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling. EMBO Rep, 2021 Jan 22;e49651.
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.
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
|
