Nuclear Organization, Dynamics and Phase Separation in Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 5142

Special Issue Editors


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Guest Editor
Department of Biology of the Cell Nucleus, Institute of Molecular Genetics of the CAS, 142 20 Prague, Czech Republic
Interests: cell nucleus; nucleolus; regulation of gene expression; epigenetics; nucleoskeleton; nuclear myosins; actin and phospholipids; lamins; laminopathies; phase separation; microscopy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Chromatin Dynamics and Metabolism in Cancer CNRS UMR9018, Institut Gustave Roussy, 39, rue Camille-Desmoulins, 94805 Villejuif, France
Interests: cell biology; hematology; molecular biology; genetics; genomics; oncology; virology; biomedicine; epigenetics; biochemistry; immunology

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Guest Editor
Head of Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Interests: medicinal chemistry; heterocyclic chemistry; organic synthesis; cancer biology; cancer cell line; pharmaceutical chemistry; anticancer compounds; apoptosis; QSAR
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are delighted to invite you to contribute to a Special Issue in Cells, which will be selected from presentations at the 27th Wilhelm Bernhard Workshop on the Cell Nucleus, taking place in Prague, 19–23 June 2023 (https://wbw27.wbworkshops.com/).

The molecular organization within the cell nucleus determines gene expression, and recent observations revolutionize our understanding how this intra-nuclear order is formed and maintained, with an emerging crucial role of phase separation. This Special Issue will address a wide range of research topics, in relation to chromatin functioning and nuclear compartmentalization in the context of regulation of gene expression, nuclear lipids, phase separation, DNA replication and repair, pathogenesis, and cancer. Attention will be awarded to multidisciplinary approaches, including light and electron (cryo)-microscopy, lipid chemistry, and biophysics, addressing novel views on the functions of macromolecular assemblies involved in nuclear compartmentalization and functioning.

Both original research manuscripts and reviews will be accepted.

Please see https://wbw27.wbworkshops.com/call-for-papers/ for more details.

We are looking forward to your contributions to this Special Issue.

Prof. Dr. Pavel Hozák
Dr. Yegor S. Vassetzky
Prof. Dr. Roman B. Lesyk
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cell nucleus
  • nuclear compartments
  • gene expression
  • nuclear lipids
  • phase separation
  • DNA replication
  • nuclear diagnostics
  • pathogenesis
  • cancer

Published Papers (4 papers)

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Research

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21 pages, 5922 KiB  
Article
Lamin A/C and PI(4,5)P2—A Novel Complex in the Cell Nucleus
by Sara Escudeiro-Lopes, Vlada V. Filimonenko, Lenka Jarolimová and Pavel Hozák
Cells 2024, 13(5), 399; https://doi.org/10.3390/cells13050399 - 25 Feb 2024
Viewed by 992
Abstract
Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a [...] Read more.
Lamins, the nuclear intermediate filaments, are important regulators of nuclear structural integrity as well as nuclear functional processes such as DNA transcription, replication and repair, and epigenetic regulations. A portion of phosphorylated lamin A/C localizes to the nuclear interior in interphase, forming a lamin A/C pool with specific properties and distinct functions. Nucleoplasmic lamin A/C molecular functions are mainly dependent on its binding partners; therefore, revealing new interactions could give us new clues on the lamin A/C mechanism of action. In the present study, we show that lamin A/C interacts with nuclear phosphoinositides (PIPs), and with nuclear myosin I (NM1). Both NM1 and nuclear PIPs have been previously reported as important regulators of gene expression and DNA damage/repair. Furthermore, phosphorylated lamin A/C forms a complex with NM1 in a phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2)-dependent manner in the nuclear interior. Taken together, our study reveals a previously unidentified interaction between phosphorylated lamin A/C, NM1, and PI(4,5)P2 and suggests new possible ways of nucleoplasmic lamin A/C regulation, function, and importance for the formation of functional nuclear microdomains. Full article
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30 pages, 4479 KiB  
Article
The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues
by Annika Schmidt, Hui Zhang, Stephanie Schmitt, Cathia Rausch, Oliver Popp, Jiaxuan Chen, Dusan Cmarko, Falk Butter, Gunnar Dittmar, Frederik Lermyte and M. Cristina Cardoso
Cells 2024, 13(2), 139; https://doi.org/10.3390/cells13020139 - 11 Jan 2024
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Abstract
Pericentric heterochromatin (PCH) forms spatio-temporarily distinct compartments and affects chromosome organization and stability. Albeit some of its components are known, an elucidation of its proteome and how it differs between tissues in vivo is lacking. Here, we find that PCH compartments are dynamically [...] Read more.
Pericentric heterochromatin (PCH) forms spatio-temporarily distinct compartments and affects chromosome organization and stability. Albeit some of its components are known, an elucidation of its proteome and how it differs between tissues in vivo is lacking. Here, we find that PCH compartments are dynamically organized in a tissue-specific manner, possibly reflecting compositional differences. As the mouse brain and liver exhibit very different PCH architecture, we isolated native PCH fractions from these tissues, analyzed their protein compositions using quantitative mass spectrometry, and compared them to identify common and tissue-specific PCH proteins. In addition to heterochromatin-enriched proteins, the PCH proteome includes RNA/transcription and membrane-related proteins, which showed lower abundance than PCH-enriched proteins. Thus, we applied a cut-off of PCH-unspecific candidates based on their abundance and validated PCH-enriched proteins. Amongst the hits, MeCP2 was classified into brain PCH-enriched proteins, while linker histone H1 was not. We found that H1 and MeCP2 compete to bind to PCH and regulate PCH organization in opposite ways. Altogether, our workflow of unbiased PCH isolation, quantitative mass spectrometry, and validation-based analysis allowed the identification of proteins that are common and tissue-specifically enriched at PCH. Further investigation of selected hits revealed their opposing role in heterochromatin higher-order architecture in vivo. Full article
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Review

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14 pages, 1702 KiB  
Review
Nuclear Phospholipids and Signaling: An Update of the Story
by Irene Casalin, Eleonora Ceneri, Stefano Ratti, Lucia Manzoli, Lucio Cocco and Matilde Y. Follo
Cells 2024, 13(8), 713; https://doi.org/10.3390/cells13080713 - 19 Apr 2024
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Abstract
In the last three decades, the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A considerable amount of interest has been raised about nuclear inositol lipids, mainly because of their role in signaling acting. Here, we review the main [...] Read more.
In the last three decades, the presence of phospholipids in the nucleus has been shown and thoroughly investigated. A considerable amount of interest has been raised about nuclear inositol lipids, mainly because of their role in signaling acting. Here, we review the main issues of nuclear phospholipid localization and the role of nuclear inositol lipids and their related enzymes in cellular signaling, both in physiological and pathological conditions. Full article
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16 pages, 1601 KiB  
Review
The Role of p53 in Nanoparticle-Based Therapy for Cancer
by Olga Szewczyk-Roszczenko and Nikolai A. Barlev
Cells 2023, 12(24), 2803; https://doi.org/10.3390/cells12242803 - 8 Dec 2023
Cited by 1 | Viewed by 1262
Abstract
p53 is arguably one of the most important tumor suppressor genes in humans. Due to the paramount importance of p53 in the onset of cell cycle arrest and apoptosis, the p53 gene is found either silenced or mutated in the vast majority of [...] Read more.
p53 is arguably one of the most important tumor suppressor genes in humans. Due to the paramount importance of p53 in the onset of cell cycle arrest and apoptosis, the p53 gene is found either silenced or mutated in the vast majority of cancers. Furthermore, activated wild-type p53 exhibits a strong bystander effect, thereby activating apoptosis in surrounding cells without being physically present there. For these reasons, p53-targeted therapy that is designed to restore the function of wild-type p53 in cancer cells seems to be a very appealing therapeutic approach. Systemic delivery of p53-coding DNA or RNA using nanoparticles proved to be feasible both in vitro and in vivo. In fact, one p53-based therapeutic (gendicine) is currently approved for commercial use in China. However, the broad use of p53-based therapy in p53-inactivated cancers is severely restricted by its inadequate efficacy. This review highlights the current state-of-the-art in this area of biomedical research and also discusses novel approaches that may help overcome the shortcomings of p53-targeting nanomedicine. Full article
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