T h e U n i v e r s i t y o f U t a h G r a d u a t e S c h o o l STATEMENT OF DISSERTATION APPROVAL The dissertation of has been approved by the following supervisory committee members: , Chair ABSTRACT The SUMO proteases SENP1 and SENP2 are known to reside at the nuclear pore complex; however, their functional roles there remain unclear. In this study, SENP1 and SENP2 are found to regulate the nuclear pore assembly of components located at the central core and cytoplasmic fibrils of the

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... r pore complex. Interestingly, SENP1 and SENP2 are found to interact with the nuclear basket component Nup153 and regulate the SUMOylation status of Nup153. The N-and C-terminal domains of Nup153 are found to mediate a bimodal interaction with SENP1/SENP2. Nup153 N-terminal is a site of SUMO modification. This modification enhances the interaction between Nup153 and SENP1/SENP2. Its C-terminal domain, on the other hand, is found to interact with SENP1/SENP2, likely through the bridging interaction mediated by the trafficking receptor Importin α. These interactions are likely to contribute to a novel function of Nup153 in NPC biogenesis. Depletion of Nup153 or SENP1/SENP2 leads to similar defects in NPC assembly of numerous nucleoporins, suggesting Nup153 and SENP1/SENP2 are likely to work in the same pathway in mediating NPC biogenesis.