Supervisor Project : Biological role and function of the ZNF451 family of SUMO E3 ligases in SUMO chain formation.
Andrea Pichler, Ph.D., is a group leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. She graduated in Molecular Biology from the University of Vienna in 1998 and did her first postdoc at the Novartis Research Institute in Vienna. In 2000 she moved to the Max Planck Institute of Biochemistry in Munich and started in Frauke Melchior´s lab her work on sumoylation. In 2006 she returned back to Vienna establishing her own group at the Max F. Perutz Laboratories mainly focusing on E2 regulation via sumoylation. Since 2010 she is back in Germany and her lab aims to understand how SUMO conjugation is regulated via E3 ligases and Ubc9 sumoylation. Recent work of her lab identified and characterized a novel class of SUMO E3 ligases, the ZNF451 family.
We identified the ZNF451 family as enzymes with SUMO2/3 paralog specific E3 ligase and E4 SUMO-chain-elongase activity that represents a model for novel SUMO conjugating enzymes. Our initial biological data indicate that the ZNF451 family functions upon stress stimulation like proteasome inhibition with MG153 or DNA damage with camptothecin (CPT), both drugs associated with SUMO chain formation. By using the SUBE and/or a combination of SUBE/TUBE pull down systems developed by the Rodriguez lab, we aim to identify ZNF451 dependent substrates specifically modified with SUMO2/3 chains and SUMO/Ub mixed chains upon stress stimulation. Identified substrates will be analysed in in vitro SUMOylation assays and diverse cell based assays by studying ZNF451 knock out cell lines and knock out cells from mice. In parallel we will design (UbiQ) and test ZNF451 family inhibitory drugs which will be analysed in comparison to ZNF451 knock out cell lines and mice.