The small protein ubiquitin is particularly famous for marking proteins for degradation but it has also been shown to regulate virtually all cellular processes. In parallel to the ubiquitin system various other ubiquitin-like modifiers have evolved, of which Fubi is particularly poorly studied despite its immunomodulatory activity.
Scientists around Malte Gersch, research group leader at the Chemical Genomics Centre at the Max Planck Institute of Molecular Physiology, have now gained first molecular insights into the machinery facilitating the Fubi-controlled maturation of a key protein of the ribosome, the cell’s protein factory. With the help of a newly developed chemical tool kit, the researchers characterized how two deubiquitinating enzymes provide specific Fubi hydrolase activity and thereby moonlight as Fubi proteases in a two-tier manner.
Fubi is produced by cells as a fusion protein with the ribosomal protein S30, and must be separated from S30 by proteases for functioning ribosomes. In immune cells, this by-product of ribosome production is utilized as a secreted signaling molecule, for example to locally reduce the activity of the maternal immune system in the uterus and to thus enable embryos to implant. How Fubi is specifically recognized by proteases and how they distinguish it from