Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2

Abstract

Numerous enzymes of the mammalian SUMO modification pathway, including two members of the SUMO protease family, SE NP2 and SE NP1, localize to the nuclear periphery. The SUMO proteases play roles both in processing SUMO during the biogenesis of this peptide moiety and also in reversing SUMO modification on specific targets to control the activities conferred by this post-translational modification. Although interaction with the C-terminal domain of the nucleoporin Nup153 is thought to contribute to SE NP2 localization at the nuclear pore complex, little is known about the binding partners of SE NP1 at the nuclear periphery. We have found that Nup153 binds to both SE NP1 and SE NP2 and does so by interacting with the unique N-terminal domain of Nup153 as well as a specific region within the C-terminal FG-rich region. We have further found that Nup153 is a substrate for sumoylation, with this modification kept in check by these two SUMO proteases. Specifically, either RNAi depletion of SE NP1/SE NP2 or expression of dominantly interfering mutants of these proteins results in increased sumoylation of endogenous Nup153. While SE NP1 and SE NP2 share many characteristics, we show here that SE NP1 levels are influenced by the presence of Nup153, whereas SE NP2 is not sensitive to changes in Nup153 abundance. © 2012 Landes Bioscience.