CHARACTERIZING THE REGULATION AND FUNCTION OF THE SUMO-SPECIFIC ISOPEPTIDASE SENP2

[摘要] The small ubiquitin-related modifier (SUMO) protein is post-translationally and covalently attached to a multitude of other proteins, regulating a plethora of essential cellular functions in the nucleus and the cytoplasm. Recent evidence links SUMO to membrane-associated functions, however, the mechanism of SUMO regulation at membranes remains largely unknown. To look at SUMO regulation, we focused on characterizing the subcellular localizations and functions of the SUMO-specific isopeptidases, collectively known as SENPs, since they comprise the largest family of SUMO proteases and are major regulators of SUMO dynamics. SENPs share a conserved C-terminal catalytic domain, but have divergent N-terminal domains containing targeting signals that determine their unique subcellular localizations and substrate specificities. In this thesis, we characterized the N-terminal domain of the mammalian SUMO-specific protease SENP2. We found that SENP2 can directly interact with intracellular membranes via a unique N-terminal amphipathic α-helix. We also show that SENP2-membrane interaction is directly regulated by Karyopherin-α (Kap-α). Furthermore, we identified SENP2 interacting proteins using BioID, which revealed that SENP2 interacts with a subset of ER-, Golgi-, and inner nuclear membrane-associated proteins. We also developed a new technique to identify SENP2 substrates. Collectively, our findings demonstrate the critical role N-terminal targeting signals play in the differential regulation of SUMO proteases, and indicate that SENP2 may play a role in regulating sumoylation at membranes.

[发布机构] Johns Hopkins University

[效力级别] SENP2

[关键词] SUMO;SENP2;Biochemistry