bims-nucpor 2023-08-13 papers

Issue of 2023–08–13
three papers selected by
Sara Mingu, Johannes Gutenberg University

FEBS Lett. 2023 Aug 07.

Puzzling out Nuclear Pore Complex assembly.

Nuclear pore complexes (NPCs) are sophisticated multiprotein assemblies embedded within the nuclear envelope and controlling the exchanges of molecules between the cytoplasm and the nucleus. In this review, we summarize the mechanisms by which these elaborate complexes are built from their subunits, the nucleoporins, based on our ever-growing knowledge of NPC structural organization and on the recent identification of additional features of this process. We present the constraints faced during the production of nucleoporins, their gathering into oligomeric complexes, and the formation of NPCs within nuclear envelopes, and review the cellular strategies at play, from co-translational assembly to the enrolment of a panel of cofactors. Remarkably, the study of NPCs can inform our perception of the biogenesis of multiprotein complexes in general - and vice versa.

Keywords: co-translational assembly; multiprotein complex assembly; nuclear envelope; nuclear pore complex; nucleoporin

DOI: https://doi.org/10.1002/1873-3468.14713

FEBS Lett. 2023 Aug 11.

Autophagy as a caretaker of nuclear integrity.

Emily Boyle, Florian Wilfling.

Due to their essential functions, dysregulation of nuclear pore complexes (NPCs) is strongly associated with numerous human diseases, including neurodegeneration and cancer[1]. On a cellular level, longevity of scaffold nucleoporins in post-mitotic cells of both C. elegans and mammals renders them vulnerable to age-related damage, which is associated with an increase in pore leakiness and accumulation of intranuclear aggregates in rat brain cells[2-4]. Thus, understanding the mechanisms which underpin the homeostasis of this complex, as well as other nuclear proteins, is essential. In this review, autophagy-mediated degradation pathways governing nuclear components in yeast will be discussed, with a particular focus on NPCs. Furthermore, the various nuclear degradation mechanisms identified thus far in diverse eukaryotes will also be highlighted. This article is protected by copyright. All rights reserved.

Keywords: Atg39; NPC-phagy; Nup159; nuclear blebbing; nuclear lamina; nuclear pore complex; nuclear-derived vesicle; nucleophagy; quality control; selective autophagy

DOI: https://doi.org/10.1002/1873-3468.14719

Cell Rep. 2023 Jul 29. pii: S2211-1247(23)00893-8. [Epub ahead of print] 112882

Nuclear transport surveillance of p53 by nuclear pores in glioblastoma.

Dini Kurnia Ikliptikawati, Nozomi Hirai, Kei Makiyama, Hemragul Sabit, Masashi Kinoshita, Koki Matsumoto, Keesiang Lim, Makiko Meguro-Horike, Shin-Ichi Horike, Masaharu Hazawa, Mitsutoshi Nakada, Richard W Wong.

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.

Keywords: 26S proteasome; CP: Cancer; CP: Molecular biology; GBM; MDM2; NUP107; p53

DOI: https://doi.org/10.1016/j.celrep.2023.112882