核孔复合物（NPCs）是核质运输的中央装置。NPCs的疾病特异性改变对于许多癌症的发病机制有所贡献；然而，在胶质母细胞瘤（GBM）中，NPCs的作用尚不清楚。在本研究中，我们报道了GBM中NPC成分NUP107的基因扩增，并显示NUP107与p53降解关键E3连接酶MDM2同时过度表达。通过抑制NUP107导致的p53蛋白稳定，可以抑制GBM细胞系的增长。机械上，NPCs通过与26S蛋白酶体相结合的出口通路建立了p53降解平台。NUP107是NPC组装的关键，NUP107的丧失会影响NPC结构的完整性，从而使26S蛋白酶体在核孔附近的比例显著降低。综上所述，我们的发现建立了NPC在运输监控中的作用，并为GBM中p53失活提供了洞察。版权所有©2023作者。由Elsevier Inc.出版。保留所有权利。

Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.