Proteasome-associated function of UCH37 is evolutionarily conserved in Plasmodium parasites

Abstract UCH37/UCHL5 is a conserved ubiquitin hydrolase with dual roles in proteasomal degradation and chromatin remodeling in humans. Its Plasmodium falciparum ortholog, PfUCH37, is essential for parasite viability and possesses both DUB and deneddylating activities. While PfUCH37 is enriched in proteasome preparations, its direct interaction and broader functions in Plasmodium remain unclear, particularly given the absence of INO80 homologs. This study utilizes transgenic parasites and proteomics to identify PfUCH37-associating proteins. We confirm a direct interaction with the proteasome and demonstrate that the interaction mechanism is evolutionarily conserved. Notably, we discover a divergence in localization compared to the human enzyme and identify novel interacting partners, suggesting alternative functions for PfUCH37 in Plasmodium. These findings provide insights into the unique biology of this essential enzyme in malaria parasites, potentially opening avenues for targeted therapeutic interventions.