Functional Specialisation of SUMO4 in Human Cell Signalling

Project title

Functional Specialisation of SUMO4 in Human Cell Signalling

Description

Cells use molecular tags to control how proteins behave. One such tag is called SUMO (Small Ubiquitin-like Modifier), which helps regulate essential processes like DNA repair, gene expression, and immune responses. Most SUMO proteins (SUMO1–3) work by attaching to other proteins — a process called SUMOylation. Disruptions in this system are linked to diseases such as cancer and inflammation. This project focuses on SUMO4, a lesser-known member of the SUMO family. Unlike its relatives, SUMO4 cannot attach to other proteins and was long thought to be inactive. However, my recent research shows that SUMO4 plays a critical role in cell signalling without needing to attach — acting instead as a “pseudoSUMO” that influences other proteins, especially SENP1, an enzyme that removes SUMO tags. Importantly, there are two common forms of SUMO4 in the human population, caused by a small genetic difference. These forms behave differently: one boosts SENP1 activity, while the other does not. This project will explore how these variants affect NFκB signalling, a key pathway in inflammation and immune responses. We will also study their impact on pancreatic beta-cells, which produce insulin and are crucial for controlling blood sugar.