bims-nucpor 2023-11-12 papers

Plant Cell. 2023 Nov 07. pii: koad282. [Epub ahead of print]

Trends Cell Biol. 2023 Nov 08. pii: S0962-8924(23)00229-5. [Epub ahead of print]

Hard to handle: how lipid saturation affects the nuclear envelope.

The nuclear envelope is a unique subdomain of the endoplasmic reticulum (ER) that encapsulates the genome and mediates communication between the nucleus and the rest of the cell via nuclear pore complexes. A recent study by Romanauska and Köhler shows that balanced lipid unsaturation is critical for nuclear envelope and nuclear pore complex architecture and function.

Keywords: GPAT; Ole1; membrane; nuclear pore complex; nucleus

DOI: https://doi.org/10.1016/j.tcb.2023.10.011

Signal Transduct Target Ther. 2023 Nov 10. 8(1): 425

Nuclear transport proteins: structure, function, and disease relevance.

Yang Yang, Lu Guo, Lin Chen, Bo Gong, Da Jia, Qingxiang Sun.

Proper subcellular localization is crucial for the functioning of biomacromolecules, including proteins and RNAs. Nuclear transport is a fundamental cellular process that regulates the localization of many macromolecules within the nuclear or cytoplasmic compartments. In humans, approximately 60 proteins are involved in nuclear transport, including nucleoporins that form membrane-embedded nuclear pore complexes, karyopherins that transport cargoes through these complexes, and Ran system proteins that ensure directed and rapid transport. Many of these nuclear transport proteins play additional and essential roles in mitosis, biomolecular condensation, and gene transcription. Dysregulation of nuclear transport is linked to major human diseases such as cancer, neurodegenerative diseases, and viral infections. Selinexor (KPT-330), an inhibitor targeting the nuclear export factor XPO1 (also known as CRM1), was approved in 2019 to treat two types of blood cancers, and dozens of clinical trials of are ongoing. This review summarizes approximately three decades of research data in this field but focuses on the structure and function of individual nuclear transport proteins from recent studies, providing a cutting-edge and holistic view on the role of nuclear transport proteins in health and disease. In-depth knowledge of this rapidly evolving field has the potential to bring new insights into fundamental biology, pathogenic mechanisms, and therapeutic approaches.

DOI: https://doi.org/10.1038/s41392-023-01649-4

Cell Chem Biol. 2023 Oct 30. pii: S2451-9456(23)00366-5. [Epub ahead of print]

Super-enhancer trapping by the nuclear pore via intrinsically disordered regions of proteins in squamous cell carcinoma cells.

Master transcription factors such as TP63 establish super-enhancers (SEs) to drive core transcriptional networks in cancer cells, yet the spatiotemporal regulation of SEs within the nucleus remains unknown. The nuclear pore complex (NPC) may tether SEs to the nuclear pore where RNA export rates are maximal. Here, we report that NUP153, a component of the NPC, anchors SEs to the NPC and enhances TP63 expression by maximizing mRNA export. This anchoring is mediated through protein-protein interaction between the intrinsically disordered regions (IDRs) of NUP153 and the coactivator BRD4. Silencing of NUP153 excludes SEs from the nuclear periphery, decreases TP63 expression, impairs cellular growth, and induces epidermal differentiation of squamous cell carcinoma. Overall, this work reveals the critical roles of NUP153 IDRs in the regulation of SE localization, thus providing insights into a new layer of gene regulation at the epigenomic and spatial level.

Keywords: BRD4; gene expression; intrinsically disordered regions; mRNA export; nuclear pore complex; p63; phase separation; squamous cell carcinoma; super-enhancer

DOI: https://doi.org/10.1016/j.chembiol.2023.10.005

PLoS Genet. 2023 Nov 10. 19(11): e1011026

Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis.

Esther Herruzo, Estefanía Sánchez-Díaz, Sara González-Arranz, Beatriz Santos, Jesús A Carballo, Pedro A San-Segundo.

The meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are localized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic trafficking and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.

DOI: https://doi.org/10.1371/journal.pgen.1011026