SUMO1/sentrin/SMT3 Specific Peptidase 3, DKFZp762A152, DKFZp586K0919, EC=3.4.22.-

SENP3 is a member of the SENP (sentrin/SUMO-specific protease) family. The SUMO protease localizes to the nucleolus and catalyzes the release of SUMO2 and SUMO3 monomers from sumoylated substrates (1,2). SENP3 has been reported responsible for the removal of SUMO2/3 from many important target proteins, and regulates their function and stability. Desumoylation of MEF2D (removal of SUMO2/3) leads to an increase of MEF2D transcriptional activation (3). SENP3 enhances the binding of HIF-1a to p300 by deconjugation of SUMO2/3 from p300, leading to the upregulation of HIF-1a transcriptional activity and angiogenesis (4). SENP3 localizes to nucleolus through its binding to the nucleolar protein nucleophosmin (NPM1) (5), and its deconjugation activity towards NPM1 is required for rRNA processing during ribosomal biogenesis (6). Under mild oxidative stress, SENP3 colocalizes with PML, and desumoylates and inhibits the function of PML to promote cell proliferation (7). SENP3 levels are tightly controlled in cells; NPM1, Arf, CHIP, and HSP90 have been shown to regulate the stability of SENP3, either by direct or indirect interaction (8,9).