Ubiquitination of proteins is a common post-translational modification; the final step of this modification is facilitated by E3 ligases. RNF19A and B are RING-between-RING (RBR) E3 ligases, that have been shown to not only ubiquitinate proteins, but also the small molecule BRD1732. Non-proteinaceous ubiquitination is a rapidly emerging area in the ubiquitin field. Studying RNF19A/B will improve our understanding of this type of ubiquitination.
Not much is known about RNF19A/B’s endogenous role in cells, their substrates, interacting partners or the pathways they regulate. Although, research so far supports roles in neurodegenerative diseases and immunity. RNF19A has been linked to familial ALS and ubiquitinates mutant SOD1, whereas RNF19B research has mainly focused on its role in immunity and natural killer (NK) cells, where it is improving pathogen clearance.
We will be applying mass spectrometry, biochemical assays and structural approaches to investigate RNF19A/B’s interaction networks, their substrates, cellular localisation and likely biological role. Using a new, mass spectrometry based method we hope to identify non-protein substrates of RNF19A and B in cells, in an unbiased fashion, to shed light on non-proteinaceous ubiquitination.
Our results may further research into neurodegenerative diseases and human immune function.