Regulation of nucleocytoplasmic transports by sumoylation

• Applicant: Professor Dr. Gabriel Schlenstedt
• Subject Area: Biochemistry
• Term: from 2013 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 235832271

The ubiquitin-like protein SUMO regulates a number of intracellular processes by altering the stability, conformation, binding activity, or localization of target proteins. SUMO is transferred posttranslationally to a lysine residue of the target protein. The SUMOylation reaction is mediated by an enzymatic cascade consisting of an activating enzyme E1, a conjugating enzyme E2, and various substrate-specific E3 ligases. This is a reversible process due to the activity of specific proteases, which cleave SUMO off its targets. We recently showed that Kap114 from Saccharomyces cerevisiae, a receptor of the importin beta family mediating protein import into the cell nucleus, is modified and regulated by SUMO. We characterized SUMO as an intranuclear cargo release factor that is in addition to the Ran GTPase required for the Kap114-mediated import pathway. Thus SUMO plays a hitherto unknown role in nucleocytoplasmic transport, which we aim to study in detail. We will particularly focus on the examination of the molecular mechanism of SUMO-induced cargo release and the involvement of additional factors in SUMO-regulated nuclear transport. Furthermore, we plan to elucidate the mechanisms of transport across the nuclear pore complexes of the SUMOylation cycle components themselves. A further goal is to find out if and how other transport receptors of the importin beta family are regulated by SUMOylation. Our methods include a combination of appropriate protein interaction studies with purified factors and localization studies of cargo and receptor molecules using wildtype and mutant strains. In our future studies, we aim to gain further insight into the functional significance of the SUMO modification for communication between the cell nucleus and the cytoplasm.

• DFG Programme: Research Grants