Stefan Mueller, Research Associate (»Add to Infobox)

Group Leader Stefan Jentsch's Group Academic: Max Planck Society for the Advancement of Science Email:  stmuellebiochem.mpg.de

General description: http://www.biochem.mpg.de/jentsch/Mueller.htm l The research interest of our group is the investigation of the ubiquitin-like SUMO system in mammals. In humans three SUMO forms are expressed from three different genes. SUMOylation targets many cellular key factors and therefore plays important roles in a broad array of cellular processes, including cell cycle control, differentiation, signal transduction and DNA repair. The currently available data suggest that SUMO regulates protein-protein interactions and in some particular cases is implicated in the regulation of subcellular localization of proteins. In my previous work with Anne Dejean (Pasteur Institute, Paris) I identified the tumour suppressor PML as a major cellular target for SUMO. We could demonstrate that the SUMO modification of PML is critical for the assembly of the so-called PML nuclear bodies suggesting that SUMO modulates the sub-cellular compartmentalization of PML and the recruitment of other components to PML NBs. In a search for other target proteins, the proto-oncogene c-Jun and the tumour suppressor p53 were shown to undergo modification by SUMO. Notably, modification of c-Jun by SUMO restrains its transcriptional activity, representing the first example of a negative regulatory function of SUMO in transcriptional processes. SUMOylation proceeds via a multistep pathway that is mechanistically analogous to ubiquitination, but uses a SUMO-specific enzymatic machinery, generally involving the dimeric AOS1/UBA2 E1 activating and the E2 enzyme Ubc9. At least in some cases E3-like activities, such as members of the Siz/PIAS protein family, the nucleoporin RanBP2 and the human polycomb group protein Pc2, stimulate the conjugation and act as specificity factors in the modification pathway. In parallel with other groups we have identified PIAS proteins as E3-like factors in the conjugation of SUMO to the proto-oncogene c-Jun and the tumour suppressor p53. One focus of our current work is to further characterize the role of PIAS in the SUMO pathway. In particular, we aim to understand the function of the PIAS/SUMO system in the control of transcriptional processes. Another focus of our work concerns the role of SUMO modification in the control of major tumour suppressor pathways, including the p53 and the retinoblastoma (pRB) tumour suppressor networks. Studying the SUMO modification of these key regulators is of general importance to understand basic mechanisms of normal cell function and may also allow deciphering an implication of the SUMO system in the pathogenesis of human malignancies, including cancer.