Grant: Operating Grant

Cancer cells need to produce many cellular components for their aberrant cell division process. These components are made from instructions encoded in genes positively regulated by a family of proteins known as E2F. To stop cell growth E2Fs need to be inhibited and this process can be reversible or irreversible. The latter prevents cancer cell growth in the long term and it is of great interest to understand its detailed mechanisms so drugs can be designed. This proposal aims to identify several components of the mechanism that permanently blocks E2F-target genes including the retinoblastoma tumor suppressor protein, the promyelocytic leukemia protein (PML) and a small protein called SUMO, that we think acts as a glue keeping together stable repressor complexes on E2F genes. We will use innovative cell culture of primary cells, gene transfer with viral vectors, novel proteomic technologies and animals models to provide a new conceptual model on the mechanisms that stably turn off E2F-target genes expecting to generate reagents, biomarkers and potential drug targets for future work.