Conserved nucleolar stress at the onset of cell death

Golstein, Pierre

doi:10.1111/febs.14095

Cited by 7 publications

(3 citation statements)

References 79 publications

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“…Second, almost all metabolic and signaling pathways in a cell are related with the nucleolus 13 . Nucleolar stress often leads to down-regulation of the nucleolar functions and a series of biological behavior changes of the cell, including disorders of protein translation, cell cycle arrest, and cell death 14 , 15 .…”

Section: Nucleolar Stress: the Canonical Patternmentioning

confidence: 99%

Nucleolar stress: is there a reverse version?

Chen

et al. 2018

J. Cancer

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The nucleolus is a dynamic structure that has roles in various physiological and pathophysiological processes. Perturbations on many aspects of the nucleolar functions are thought to cause “nucleolar stress”, which occurs in response to a variety of chemotherapeutic drugs. The main characteristic changes of nucleolar stress include: 1) reduction of the size and volume of the nucleolus; 2) inhibition of RNA Pol I-mediated rRNA synthesis; and 3) nucleoplasmic translocation of nucleolar stress-related proteins. In studying the apoptosis-inducing effect of the natural compound lovastatin (LV) on breast cancer stem cells, we unexpectedly uncovered a novel form of nucleolar stress, which we call “reverse nucleolar stress”. In our system, the canonical nucleolus stress inducer doxorubicin caused nucleoplasmic translocation of the nucleolar protein NPM and complete abolishment of Nolc1, an NPM-interacting protein and an activator of rRNA transcription. In contrast, the reverse nucleolar stress induced by LV is manifested as a more localized perinucleolar distribution of NPM and an increase in the protein level of Nolc1. Furthermore, translocation of the ribosomal protein RPL3 from the cytoplasm to the nucleolus and increased AgNOR staining were observed. These changes characterize a novel pattern of nucleolar stress doubtlessly distinguishable from the canonical one. The functional consequences of reverse nucleolar stress are not clear at present but may presumably be related to cell death or even normalization of the stressed cell. The discovery of reverse nucleolar stress opens up a new area of research in molecular and cellular biology and might have important implications in cancer therapy.

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Section: Nucleolar Stress: the Canonical Patternmentioning

confidence: 99%

Nucleolar stress: is there a reverse version?

Chen

et al. 2018

J. Cancer

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“…For instance, Dictyostelium has been used to study cell shape regulation during cytokinesis and the involvement of cyclin-dependent kinases and their associated cyclins in cell cycle control (Huber, 2014;Srivastava, Iglesias, & Robinson, 2016). Dictyostelium has also been useful for studying DNA repair mechanisms and the conserved role of the nucleolus in regulating the onset of cell death in eukaryotic cells (Golstein, 2017;Pears & Lakin, 2014). However, perhaps its most significant contribution is tied to its use as a model system for studying cell migration, which underlies many fundamental processes in mammals including embryogenesis and wound healing.…”

Section: Using Dictyostelium To Study Conserved Cellular and Developm...mentioning

confidence: 99%

Dictyostelium discoideum: A Model System for Cell and Developmental Biology

Mathavarajah

Flores

Huber

2017

CP Essential Lab Tech

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The social amoeba Dictyostelium discoideum has long served as a model system for studying fundamental processes in cell and developmental biology. This eukaryotic microbe is also recognized as a model organism for biomedical and human disease research since the genome encodes homologs of genes linked to human disease, such as those linked to cancer and neurodegeneration. Dictyostelium has a unique life cycle composed of a unicellular growth phase and a multicellular developmental phase that is induced by starvation. During its life cycle, Dictyostelium undergoes conserved cellular processes including, but not limited to, cell proliferation, phagocytosis, intercellular signaling, cell adhesion and motility, chemotaxis, and cell differentiation. The history of the organism, the resources available to researchers in the community, and the diverse ways that Dictyostelium is used in the contemporary research lab are discussed. © 2017 by John Wiley & Sons, Inc.

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“…Since ribosome biosynthesis is a driving force for cancer cells, they are more susceptible to disruption of ribosome production than normal cells, and this susceptibility is used to combat them (Bywater et al 2012 ). A growing body of evidence suggests that disorder of nucleoli is a conservative mechanism leading to developmental cell death at least in certain cell types of multicellular organisms, including animals and plants, as well as in eukaryotic protist Dictyostelium (Golstein 2017 ; Luciani et al 2016 ). In this context, natural or intentional disruption of nucleolar morphology and/or functioning can provoke death of eukaryotic cells, including cancer ones.…”

Section: Introductionmentioning

confidence: 99%

The nucleolus, an ally, and an enemy of cancer cells

Stępiński

2018

Histochem Cell Biol

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The rates of ribosome production by a nucleolus and of protein biosynthesis by ribosomes are tightly correlated with the rate of cell growth and proliferation. All these processes must be matched and appropriately regulated to provide optimal cell functioning. Deregulation of certain factors, including oncogenes, controlling these processes, especially ribosome biosynthesis, can lead to cell transformation. Cancer cells are characterized by intense ribosome biosynthesis which is advantageous for their growth and proliferation. On the other hand, this feature can be engaged as an anticancer strategy. Numerous nucleolar factors such as nucleolar and ribosomal proteins as well as different RNAs, in addition to their role in ribosome biosynthesis, have other functions, including those associated with cancer biology. Some of them can contribute to cell transformation and cancer development. Others, under stress evoked by different factors which often hamper function of nucleoli and thus induce nucleolar/ribosomal stress, can participate in combating cancer cells. In this sense, intentional application of therapeutic agents affecting ribosome biosynthesis can cause either release of these molecules from nucleoli or their de novo biosynthesis to mediate the activation of pathways leading to elimination of harmful cells. This review underlines the role of a nucleolus not only as a ribosome constituting apparatus but also as a hub of both positive and negative control of cancer development. The article is mainly based on original papers concerning mechanisms in which the nucleolus is implicated directly or indirectly in processes associated with neoplasia.

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Conserved nucleolar stress at the onset of cell death

Cited by 7 publications

References 79 publications

Nucleolar stress: is there a reverse version?

Nucleolar stress: is there a reverse version?

Dictyostelium discoideum: A Model System for Cell and Developmental Biology

The nucleolus, an ally, and an enemy of cancer cells

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