C 1: Multiple mechanisms controlling the SUMO modified state of proteins
Prof. Dr. Jürgen Dohmen
Institut für Genetik, Universität zu Köln
email: j.dohmen@uni-koeln.de
phone: +49-(0)221 470 4862
website
Running time: 2003 – 2011
Abstract
Posttranslational protein modification with SUMO is an important regulatory mechanism implicated in many cellular processes. We identified two yeast SUMO binding proteins that mediate the proteolytic downregulation of sumoylated proteins. Poly-sumoylation and ubiquitin-dependent degradation appear to be alternative mechanisms to inactivate sumoylated proteins. Inhibition of both mechanisms leads to severe phenotypic defects. Proteolytic control of SUMO conjugates is conserved from yeast to humans. We will analyse the mechanistic details and functions of ubiquitin-mediated proteolysis of SUMO substrates.
(A final report will follow.)
Publications resulting from the project:
Schnellhardt, M., Uzunova, K., Bade, V.N., Krause, A., Weisshaar, S.R. Praefcke, G.J.,K., and Dohmen, R.J. (2012). Analysis of cellular SUMO and SUMO-ubiquitin hybrid conjugates. Methods in Molecular Biology 832, 82-91. (review)
Praefcke, G.J,K, Hofmann, K., and Dohmen, R.J. (2012). SUMO playing tag with ubiquitin. Trends in Biochemical Sciences 37, 23-11. (review)
Hermkes, R., Fu, Y.F., Nürrenberg, K., Budhiraja, R., Schmelzer, E., Elrouby, N., Dohmen, R.J., Bachmair, A., and Coupland, G. (2011). Distinct roles for Arabidopsis SUMO protease ESD4 and its closest homolog ELS1. Planta 233, 63-73.
Miteva, M., Keusekotten, K., Hofmann, K., Praefcke, G.J.K., and Dohmen, R.J. (2010). Sumoylation as a signal for polyubiquitylation and proteasomal degradation. In: Conjugation and decon-jugation of ubiquitin family modifiers, edited by Marcus Groettrup. Landes Bioscience and Springer Science+Business Media. pp 195-214.
Weisshaar, S.R., Keusekotten, K., Krause, A., Horst, C., Springer, H.M., Göttsche, K., Dohmen, R.J., and Praefcke, G.J.K. (2008). Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML. FEBS Lett. 582, 3174-3178.
Uzunova, K., Göttsche, K., Miteva, M., Weisshaar, S.R., Glanemann, C., Schnellhardt, M., Niessen, M., Scheel, H., Hoffmann, K., Johnson, E.S., Praefcke, G.J.K. and Dohmen, R.J. (2007). Ubiquitin-dependent Proteolytic control of SUMO conjugates. J. Biol. Chem. 282, 34167-34175.