For a long time, it was believed that the primary role of peptides produced by proteasomes was to help T cells in the immune system recognize and attack foreign invaders. However, it remains unclear whether these peptides have additional roles in fighting infections.
We know that antimicrobial peptides serve as the body’s first line of defense against pathogens, even before the immune system is fully activated. While their protective roles in various tissues are well recognized, the mechanisms behind their production are not yet fully understood.
Recent discoveries have shown that proteasomes contribute to the generation of these defense peptides, particularly in response to bacterial presence. These peptides can disrupt bacterial membranes, inhibiting bacterial growth both in laboratory conditions and in living organisms.
Many of these potential defense peptides are positively charged, suggesting they may be produced during proteasomal degradation as an initial barrier against infection. Moreover, bacterial invasion appears to alter proteasome activity, enhancing their ability to produce antimicrobial peptides.
Interestingly, since neuroendocrine tumor (NET) cells are also considered foreign by the body, the same or related proteasomes may produce anti-cancer peptides that are potentially specific to different types of NETs.
This research not only highlights the role of proteasomes in immune defense but also suggests they may have additional, previously unrecognized functions. From a practical perspective, identifying proteasome-derived peptides could lead to the development of new, highly specific biomarkers for detecting certain infections or cancers.
Goldberg et al. Cell-autonomous innate immunity by proteasome-derived defense peptides. Nature volume 639, pages1032–1041 (2025)