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.