Detailed proximal protein profiling of endogenous p53 in colon cancer cells

01 January 2019 → 31 December 2019
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Morphological sciences
    • Oncology
    • Morphological sciences
    • Oncology
    • Morphological sciences
    • Oncology
colon cancer
Project description

It remains a tremendous challenge to map the protein complexes in the cell. Mapping these
complexes is important since they are essentially the machines that perform all the processes within
the cell. Despite over 30 methods currently available, there is still no single approach that can be
applied for all types of interactions between proteins. In this project we study the TP53 gene. a gene
that is mutated in over 50% of all cancers and that has been studied for almost 40 years. This has
resulted in an intricate network around the gene product, the p53 protein. However, some
important questions still remain in the field. For example, the actual composition of the p53
complexes is considered as one of the major short term goals, not in the least because this would
aid significantly for the therapeutic targeting of the protein. We have recently applied the BioID
protein complex mapping technology on the p53 protein. Unlike all other researchers who use
artificial constructs for this approach, we have deployed this powerful method on the endogenous
p53 protein via the CRISPR-Cas9 technology. This allowed an unprecedented and accurate view on
the p53 complex which will push knowledge of these complexes to a new level of detail. In this
project we want to investigate the endogenous p53 complex when we introduce the mutations that
occur in (colon cancer) patients. In addition we will use this novel tool to assess the effect of
candidate p53 drugs on the complex.