Regulation of cell death decisions

Within our subproject, we aim to understand how tumor cells decide cell fate in response to errors during cell division (mitosis). We will focus on the role of the most prominent tumor suppressor, p53, and one of its upstream regulators, a protease termed caspase-2. Based on genetic screens already conducted in our laboratory, we have identified a number of candidate genes that may impact this cell death / survival decision in response to mitotic errors. To define the contribution of these genes to the decision making process, together with our colleagues in this SFB-initiative (TRR353), we will conduct a series of cell biological experiments, supported by transcriptome and proteome analyses. The role of p53 as a key tumor suppressor is undisputed. Moreover, p53 is critical for the efficacy of a broad array of tumor therapeutics. However, p53 is lost in many cancers and hence targeting tumors that lack p53 function is critical to improve anticancer therapy. Our studies are geared to improved our understanding of these processes with the long term perspective to provide novel opportunities to target p53-deficient malignancies.