Post translational modifications play a very important role in the fine tuning of protein function. These modifications can consist in the addition of small chemical groups or the covalent attachment of other small proteins. Among the small proteins that can be attached to other proteins, the most relevant one is ubiquitin.
Ubiquitin signaling is involved in practically every single cellular process, having a very high importance in the regulation of the DNA damage response. The DNA damage response consists of the plethora of signaling pathways and enzymatic activities that cells are endorsed with in order to overcome the different sources of DNA damage that challenge the integrity of their genomes.
Deficiencies in the DNA damage response cause genome instability, which is one of the hallmarks of cancer.
Ubiquitination consists of a cascade reaction performed by the so called E1, E2 and E3 enzymes. More than 600 E3 enzymes are encoded in the human genome. In the lab, we combine mass-spectrometry based proteomics approaches to identify E3-specific ubiquitination substrates with molecular biology, biochemistry and cell biology techniques to unravel the role of ubiquitination on the regulation of these ubiquitinated proteins.
The aim of our research is to discover new components of the DNA damage response machinery that could become targets of anti-cancer treatments in the future.