3rd Ubiquitin Function in Health and Disease

We have reached a fascinating point in our research on the ubiquitin system’s function, physiology and roles in disease. The attachment of ubiquitin to a protein in the cytosol was first identified as a means to enable degradation of proteins in the cytosol by the proteasome. It was much later that it was discovered that the ubiquitin system fulfils another crucial cellular function: through the dynamics offered by ubiquitination and subsequent deubiquitination it gives a multitude of signalling pathways the required plasticity to initiate but also to limit their signalling output in an exquisitely controlled manner. Whereas certain signalling-related functions employ ubiquitin’s proteasome-targeting function, e.g. the activation of NF-kB following degradation of I-kB, most signalling-related functions of the ubiquitin system are mediated by different types of ubiquitin chains acting as scaffolds for the recruitment of signalling modules to protein complexes which serve as platforms for the triggering of specific signalling complexes.