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      The Biology of the Nuclear Envelope and Its Implications in Cancer Biology

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          Abstract

          The formation of the nuclear envelope and the subsequent compartmentalization of the genome is a defining feature of eukaryotes. Traditionally, the nuclear envelope was purely viewed as a physical barrier to preserve genetic material in eukaryotic cells. However, in the last few decades, it has been revealed to be a critical cellular component in controlling gene expression and has been implicated in several human diseases. In cancer, the relevance of the cell nucleus was first reported in the mid-1800s when an altered nuclear morphology was observed in tumor cells. This review aims to give a current and comprehensive view of the role of the nuclear envelope on cancer first by recapitulating the changes of the nuclear envelope during cell division, second, by reviewing the role of the nuclear envelope in cell cycle regulation, signaling, and the regulation of the genome, and finally, by addressing the nuclear envelope link to cell migration and metastasis and its use in cancer prognosis.

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          Most cited references193

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          Insulin-like growth factors and their binding proteins: biological actions.

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            Identification of long-lived proteins reveals exceptional stability of essential cellular structures.

            Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell's life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process. PAPERCLIP: Copyright © 2013 Elsevier Inc. All rights reserved.
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              Molecular mechanisms underlying RB protein function.

              Inactivation of the RB protein is one of the most fundamental events in cancer. Coming to a molecular understanding of its function in normal cells and how it impedes cancer development has been challenging. Historically, the ability of RB to regulate the cell cycle placed it in a central role in proliferative control, and research focused on RB regulation of the E2F family of transcription factors. Remarkably, several recent studies have found additional tumour-suppressor functions of RB, including alternative roles in the cell cycle, maintenance of genome stability and apoptosis. These advances and new structural studies are combining to define the multifunctionality of RB.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 May 2019
                May 2019
                : 20
                : 10
                : 2586
                Affiliations
                [1 ]Molecular Pathology, Department of Translational Medicine, Lund University, Skåne University Hospital, 20502 Malmö, Sweden; maria.alvarado-kristensson@ 123456med.lu.se
                [2 ]Laboratory of Molecular Cell Biomedicine, University of the Balearic Islands, 07121 Palma de Mallorca, Spain
                [3 ]Lipopharma Therapeutics, Isaac Newton, 07121 Palma de Mallorca, Spain
                Author notes
                [* ]Correspondence: ca.rossello@ 123456uib.es or ca.rossello@ 123456lipopharma.com ; Tel.: +34-971-173-331
                Author information
                https://orcid.org/0000-0003-0598-7986
                https://orcid.org/0000-0002-8977-607X
                Article
                ijms-20-02586
                10.3390/ijms20102586
                6566445
                31137762
                4910c059-8fbb-4d95-ac14-81cb527d3da1
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 March 2019
                : 25 May 2019
                Categories
                Review

                Molecular biology
                nucleus,envelope,γ-tubulin,mitosis,cell cycle,signaling,genome,cancer,diagnosis,metastasis
                Molecular biology
                nucleus, envelope, γ-tubulin, mitosis, cell cycle, signaling, genome, cancer, diagnosis, metastasis

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