Supervisor Project : Biological role and function of the ZNF451 family of SUMO E3 ligases in SUMO chain formation.
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.