Protein degradation is crucial for maintaining the correct levels of protein inside a cell. A major route of protein degradation is via the proteasome, which recognises proteins destined for degradation via their ubiquitin tags. Oxidised proteins can also be degraded by the proteasome independent of a ubiquitin tag.
In addition to maintaining protein homeostasis, the proteasome plays a critical role in immune surveillance by degrading undesired or damaged proteins into smaller peptides that can be displayed on a cell’s surface to activate T cells. Since this is the mechanism by which the body’s immune system can recognise cancerous cells, understanding more about how the proteasome processes different types of cellular proteins may provide opportunities to exploit this system therapeutically.
In mammalian cells, there are four subtypes of proteasome: the standard proteasome; the immunoproteasome; and two intermediate proteasomes. However, it is still unclear how these subtypes differ in their efficiency to degrade ubiquitinated or oxidised proteins. In this paper published in the journal Scientific Reports, a team from Professor Benoit Van den Eynde’s laboratory in Brussels, performed a side-by-side comparison of the four proteasome subtypes. Their results showed that all four subtypes were equally able to degrade ubiquitinated proteins but that the standard proteasome subtype was less able to degrade oxidised proteins.
This study therefore sheds more light on the mechanism of processing proteins to peptides for display on the cell surface, including in cancer cells.