Prof. Dr. Jürgen Dohmen

Institute for Genetics

IGSDHD Faculty

Zuelpicher Str. 47a
Gebäude: 301
Zimmer: 2nd floor
50674 Cologne

Project proposals in Ubiquitin family modifiers and the proteasome

Posttranslational modifications such as ubiquitylation and sumoylation are versatile tools of eukaryotic cells to regulate protein functions.1 One of the most important functions of ubiquitylation is that it targets protein for degradation by the 26S proteaome.2 However, some proteins such as the ornithine decarboxylase are also degraded by the proteasome in a ubiquitin independent manner.3-5 We are interested in understanding the different modes of substrate recognition by the proteasome. Modification with the small ubiquitin family modifier SUMO has many and essential functions as well.1 We have recently discovered that poly-sumoylation serves a role as a primary targeting signal for ubiquitin-dependent proteasomal degradation.1,6,7 This function is mediated by a novel class of RING finger ubiquitin ligases containing multiple SUMO interacting motifs (SIMs). We identified two such ubiquitin ligases (Slx5- Slx8 and Uls1/Ris1) in Saccharomyces cerevisiae.6 We are interested in understanding the mechanistic details and cellular functions of this targeting mechanism and its variations in mammalian cells.7 The 26S proteasome is the central protease mediating protein degradation in the cytosol and nucleus of eukaryotic cells.2 We are investigating how biogenesis of this complex 2MDa protease is regulated and orchestrated by dedicated chaperones.2,8,9 PhD projects on these subjects are available in our group.

Selected relevant Publications from our group:
1Praefcke, G.J,K, Hofmann, K., and Dohmen, R.J. (2012) SUMO playing tag with ubiquitin. Trends. Biochem. Sci, 37, 23-11.
2Marques, A.J., Palanimurugan, R., Matias, A.C., Ramos, P.C., and Dohmen, R.J. (2009) Catalytic Mechanism and Assembly of the Proteasome. Chem. Rev. 109, 1509-1536.
3Palanimurugan, R., Scheel, H., Hofmann, K., and Dohmen, R.J. (2004) Polyamines regulate their synthesis by inducing expression and blocking degradation of ODC antizyme. EMBO J. 23, 4857-4867.
4Gödderz, D., Schäfer, E., Palanimurugan, R., Dohmen, R.J. (2011). The N-terminal unstructured domain of yeast ODC functions as a transplantable and replaceable ubiquitin-independent degron. J. Mol. Biol. 407, 354-367.
5Kurian, L., Palanimurugan, R., Gödderz, D., and Dohmen RJ. (2011). Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding of its mRNA. Nature 477, 490-494.
6Uzunova, K., Göttsche, K., Miteva, M., Weisshaar, S.R., Glanemann, Schnellhardt, M., Niessen, M., C.,Scheel, H., Hoffmann, K., Johnson, E.S., Praefcke, G.J.K. and Dohmen, R.J. (2007). Ubiquitindependent Proteolytic control of SUMO conjugates. J. Biol. Chem. 282, 34167-34175.
7Weisshaar, S.R., Keusekotten, K., Krause, A., Horst, C., Springer, H.M., Göttsche, K., Dohmen, R.J. and Praefcke, G.J. (2008). Arsenic trioxide stimulates SUMO-2/3 modification leading to RNF4-dependent proteolytic targeting of PML. FEBS Lett. 582, 3174-3178.
8Ramos, P.C., Höckendorff, J., Johnson, E., Varshavsky, A., and Dohmen, R.J. (1998) Ump1p is required for maturation of the 20S proteasome, and becomes its substrate upon completion of the assembly. Cell 20, 489-499.
9Ramos, P.C., and Dohmen, R.J. (2008). PACemakers of proteasome core particle assembly. Structure 16, 1296-304.

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