SENP3

SUMO-specific protease 3 (SENP3) is a human enzyme belonging to the SENP family that processes SUMO precursors and removes SUMO from substrate proteins. It shows a preference for SUMO2/3 over SUMO1 and is primarily localized in the nucleolus and nucleus, with expression across many tissues.

Biochemically, SENP3 is a cysteine protease; like other SENPs, it contains a catalytic domain with a cysteine-histidine-aspartate triad that catalyzes SUMO hydrolysis. It participates in maturation of SUMO2/3 and catalyzes deSUMOylation of substrates, thereby regulating the SUMOylation status of proteins involved in ribosome biogenesis and nucleolar function.

Biological roles include regulation of ribosome biogenesis in the nucleolus, where SENP3 deSUMOylates nucleolar proteins such as nucleophosmin (NPM1) and fibrillarin, influencing rRNA transcription and ribosomal assembly. It also engages in cellular stress responses; oxidative stress can modulate SENP3 stability and localization, altering SUMOylation patterns and signaling pathways such as p53.

Regulation and interactions involve modulation by the cellular redox state and post-translational modifications; SENP3 may accumulate in response to oxidative stress, affecting nucleolar SUMO dynamics. It interacts with components of the SUMO machinery and nucleolar regulators.

Clinical and research context notes that dysregulation of SENP3 or the SUMO pathway has been linked to various diseases, including cancer and neurodegenerative conditions. Ongoing research aims to map SENP3 substrates and regulatory networks and to understand how redox signaling controls its function.