Desubiquitinantes

Desubiquitinantes, commonly known as deubiquitinases (DUBs), are enzymes that remove ubiquitin moieties from substrate proteins, thereby regulating ubiquitination status and influencing protein stability, localization, and activity. They belong to several distinct families, including ubiquitin-specific proteases (USPs), ubiquitin C-terminal hydrolases (UCHs), ovarian tumor proteases (OTUs), Machado–Joseph disease protein domain proteases (MJD), and Josephin domain proteases, each characterized by unique catalytic domains and substrate preferences. DUBs share a conserved cysteine or histidine catalytic residue that orchestrates nucleophilic attack on the isopeptide bond linking ubiquitin to lysine residues or the C‑terminal glycine of ubiquitin, releasing free ubiquitin and a deubiquitinated protein.

The enzymatic activity of desubiquitinantes counterbalances the action of E1 activating enzymes, E2 conjugating enzymes, and E3 ligases, maintaining cellular ubiquitin pools and ensuring proper signaling pathways. They are involved in diverse cellular processes such as DNA repair, cell cycle control, transcriptional regulation, and signal transduction. Dysregulation of DUB activity has been implicated in various pathologies, including cancer, neurodegenerative disorders, and autoimmune diseases. Consequently, several DUB inhibitors are under investigation as therapeutic agents; for instance, the USP7 inhibitor P22077 has shown efficacy in preclinical tumor models, while the OTUB1 inhibitor G9 blocks viral replication in infected cells.

Research into desubiquitinantes continues to reveal intricacies of post‑translational modification networks, underscoring their pivotal role in protein homeostasis. Advances in structural biology, high‑throughput screening, and chemical biology contribute to a deeper understanding of DUB specificity and regulation, offering prospects for targeted drug discovery and precision medicine.