Nuclear transport surveillance of p53 by nuclear pores in glioblastoma

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

doi:10.1016/j.celrep.2023.112882

Cited by 8 publications

(3 citation statements)

References 82 publications

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“…We and others have demonstrated the crucial involvement of NPC transcription enhancer proteins in several types of cancer [39,40]. We demonstrated the involvement of the nuclear pore protein Tpr in autophagy a decade ago, a process that has recently had implications for ependymoma [38].…”

Section: Introductionmentioning

confidence: 71%

“…Various models for the trafficking of FG-Nups have been suggested, including the spider cobweb, forest, virtual gating, polymer brush, and selective phase/hydrogel models [19,30]. The malfunctioning of the NPC transport mechanism is linked to a variety of illnesses, including neurodegeneration [31], viral infections [32][33][34][35][36][37], and cancer [38,39].…”

Section: Introductionmentioning

confidence: 99%

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An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy

Qiu,

Sajidah,

Kondo

et al. 2024

Cells

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Nuclear pore complexes (NPCs) on the nuclear membrane surface have a crucial function in controlling the movement of small molecules and macromolecules between the cell nucleus and cytoplasm through their intricate core channel resembling a spiderweb with several layers. Currently, there are few methods available to accurately measure the dynamics of nuclear pores on the nuclear membranes at the nanoscale. The limitation of traditional optical imaging is due to diffraction, which prevents achieving the required resolution for observing a diverse array of organelles and proteins within cells. Super-resolution techniques have effectively addressed this constraint by enabling the observation of subcellular components on the nanoscale. Nevertheless, it is crucial to acknowledge that these methods often need the use of fixed samples. This also raises the question of how closely a static image represents the real intracellular dynamic system. High-speed atomic force microscopy (HS-AFM) is a unique technique used in the field of dynamic structural biology, enabling the study of individual molecules in motion close to their native states. Establishing a reliable and repeatable technique for imaging mammalian tissue at the nanoscale using HS-AFM remains challenging due to inadequate sample preparation. This study presents the rapid strainer microfiltration (RSM) protocol for directly preparing high-quality nuclei from the mouse brain. Subsequently, we promptly utilize HS-AFM real-time imaging and cinematography approaches to record the spatiotemporal of nuclear pore nano-dynamics from the mouse brain.

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Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy

Qiu,

Sajidah,

Kondo

et al. 2024

Cells

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“…Cells for immunofluorescence (IF) analysis were treated as previously reported [ 24 ]. Briefly, cells on coverslips were fixed for 10 min in 4% paraformaldehyde diluted in PBS for 10 min, then permeabilized with 0.3% Triton X-100 in PBS for 3 min at RT and blocked with PBS containing 4% bovine serum albumin (BSA) and 0.1% Tween-20.…”

Section: Methodsmentioning

confidence: 99%

Phase-separated super-enhancers confer an innate radioresistance on genomic DNA

Matsumoto,

Ikliptikawati,

Makiyama

et al. 2024

Journal of Radiation Research

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Recently, biomolecular condensates formed through liquid–liquid phase separation have been widely reported to regulate key intracellular processes involved in cell biology and pathogenesis. BRD4 is a nuclear protein instrumental to the establishment of phase-separated super-enhancers (SEs) to direct the transcription of important genes. We previously observed that protein droplets of BRD4 became hydrophobic as their size increase, implying an ability of SEs to limit the ionization of water molecules by irradiation. Here, we aim to establish if SEs confer radiation resistance in cancer cells. We established an in vitro DNA damage assay that measures the effect of radicals provoked by the Fenton reaction on DNA integrity. This revealed that DNA damage was markedly reduced when BRD4 underwent phase separation with DNA. Accordingly, co-focal imaging analyses revealed that SE foci and DNA damage foci are mutually exclusive in irradiated cells. Lastly, we observed that the radioresistance of cancer cells was significantly reduced when irradiation was combined with ARV-771, a BRD4 de-stabilizer. Our data revealed the existence of innately radioresistant genomic regions driven by phase separation in cancer cells. The disruption of these phase-separated components enfolding genomic DNA may represent a novel strategy to augment the effects of radiotherapy.

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Advances in the understanding of nuclear pore complexes in human diseases

Li,

Zhu,

Zhai

et al. 2024

J Cancer Res Clin Oncol

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Background Nuclear pore complexes (NPCs) are sophisticated and dynamic protein structures that straddle the nuclear envelope and act as gatekeepers for transporting molecules between the nucleus and the cytoplasm. NPCs comprise up to 30 different proteins known as nucleoporins (NUPs). However, a growing body of research has suggested that NPCs play important roles in gene regulation, viral infections, cancer, mitosis, genetic diseases, kidney diseases, immune system diseases, and degenerative neurological and muscular pathologies. Purpose In this review, we introduce the structure and function of NPCs. Then We described the physiological and pathological effects of each component of NPCs which provide a direction for future clinical applications. Methods The literatures from PubMed have been reviewed for this article. Conclusion This review summarizes current studies on the implications of NPCs in human physiology and pathology, highlighting the mechanistic underpinnings of NPC-associated diseases.

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Nuclear transport surveillance of p53 by nuclear pores in glioblastoma

Cited by 8 publications

References 82 publications

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy

An Efficient Method for Isolating and Purifying Nuclei from Mice Brain for Single-Molecule Imaging Using High-Speed Atomic Force Microscopy

Phase-separated super-enhancers confer an innate radioresistance on genomic DNA

Advances in the understanding of nuclear pore complexes in human diseases

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