The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish

Paridaen, Judith T.M.L.; Janson, Esther; Utami, Kagistia Hana; Pereboom, Tamara C.; Essers, Paul; Rooijen, Carina van; Živković, Danica; MacInnes, Alyson W.

doi:10.1016/j.ydbio.2011.04.028

Cited by 39 publications

(35 citation statements)

References 51 publications

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“…There are some studies that addressed this question by investigating the effect of nucleostemin depletion in cells with wild-type and mutant p53, but they reached opposite conclusions. In support of the p53-dependency of nucleostemin activity, it has been shown that cell cycle arrest or apoptosis that is triggered by knockdown or knockout of nucleostemin can be completely or partially reversed by p53 knockdown (Ma and Pederson, 2007;Paridaen et al, 2011;Yamashita et al, 2013). Furthermore, nucleostemin has been found to directly interact with MDM2 to modulate the activity of p53 (Dai et al, 2008;Meng et al, 2008).…”

Section: Anole (46%)mentioning

confidence: 93%

Turning a new page on nucleostemin and self-renewal

Tsai

2014

Journal of Cell Science

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A quintessential trait of stem cells is embedded in their ability to selfrenew without incurring DNA damage as a result of genome replication. One key self-renewal factor is the nucleolar GTPbinding protein nucleostemin (also known as guanine-nucleotidebinding protein-like 3, GNL3, in invertebrate species). Several studies have recently pointed to an unexpected role of nucleostemin in safeguarding the genome integrity of stem and cancer cells. Since its discovery, the predominant presence of nucleostemin in the nucleolus has led to the notion that it might function in the cardcarrying event of the nucleolus -the biogenesis of ribosomes. As tantalizing as this might be, a ribosomal role of nucleostemin is refuted by evidence from recent studies, which argues that nucleostemin depletion triggers a primary event of DNA damage in S phase cells that then leads to ribosomal perturbation. Furthermore, there have been conflicting reports regarding the p53 dependency of nucleostemin activity and the cell cycle arrest profile of nucleostemindepleted cells. In this Commentary, I propose a model that explains how the many contradictory observations surrounding nucleostemin can be reconciled and suggest that this protein might not be as multitasking as has been previously perceived. The story of nucleostemin highlights the complexity of the underlying molecular events associated with the appearance of any cell biological phenotype and also signifies a new understanding of the genome maintenance program in stem cells.

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Section: Anole (46%)mentioning

confidence: 93%

Turning a new page on nucleostemin and self-renewal

Tsai

2014

Journal of Cell Science

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“…We have studied its expression in order to characterize in more detail the epigenetic state of the RPE. Nucleostemin (a marker of low-differentiated cells) has been identified in pluripotent embryonic stem cells and low-differentiated neural cells in both vertebrates and invertebrates [112,113,114,115]. It has various functions and is involved in the regulation of RNA polymerase I activity, transcription, chromatin structure, etc.…”

Section: Epigenetic Factors In Cell Of Normal Rpe and At Early Stamentioning

confidence: 99%

Cellular and Molecular Preconditions for Retinal Pigment Epithelium (RPE) Natural Reprogramming during Retinal Regeneration in Urodela

Grigoryan

Markitantova

2016

Biomedicines

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Many regeneration processes in animals are based on the phenomenon of cell reprogramming followed by proliferation and differentiation in a different specialization direction. An insight into what makes natural (in vivo) cell reprogramming possible can help to solve a number of biomedical problems. In particular, the first problem is to reveal the intrinsic properties of the cells that are necessary and sufficient for reprogramming; the second, to evaluate these properties and, on this basis, to reveal potential endogenous sources for cell substitution in damaged tissues; and the third, to use the acquired data for developing approaches to in vitro cell reprogramming in order to obtain a cell reserve for damaged tissue repair. Normal cells of the retinal pigment epithelium (RPE) in newts (Urodela) can change their specialization and transform into retinal neurons and ganglion cells (i.e., actualize their retinogenic potential). Therefore, they can serve as a model that provides the possibility to identify factors of the initial competence of vertebrate cells for reprogramming in vivo. This review deals mainly with the endogenous properties of native newt RPE cells themselves and, to a lesser extent, with exogenous mechanisms regulating the process of reprogramming, which are actively discussed.

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“…During neural lineage commitment there is no direct evidence that rRNA transcription is inhibited; it is likely, however, that mechanisms involving nucleolar dynamics could be in play. For example in brain and retina the levels of the nucleolar protein nucleostemin, a controller of pre-rRNA processing, are rapidly reduced before cell cycle exit and neural differentiation [4, 5], suggesting that rRNA biosynthesis may have a regulatory effect on neurogenesis.…”

Section: Non-traditional Roles Of the Nucleolus Under Physiological Cmentioning

confidence: 99%

Nucleolar activity in neurodegenerative diseases: a missing piece of the puzzle?

Parlato

Kreiner

2012

J Mol Med

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Nucleoli are the sites where synthesis of rRNA and ribosomal assembly take place. Along with these "traditional" roles, the nucleolus controls cellular physiology and homeostasis. The cellular and molecular alterations associated with impaired nucleolar activity ("nucleolar stress") have just started to be systematically explored in the nervous system taking advantage of newly available animal models lacking rRNA synthesis in specific neurons. These studies showed that nucleolar function is necessary for neuronal survival and that its modality of action differs between and within cell types. Nucleolar function is also crucial in pathology as it controls mitochondrial activity and critical stress signaling pathways mimicking hallmarks of human neurodegenerative diseases. This mini-review will focus on the modes of action of nucleolar stress and discuss how the manipulation of nucleolar activity might underscore novel strategies to extend neuronal function and survival.Keywords rRNA . Nucleolus . Cellular stress . Neurodegeneration . Mouse models Non-traditional roles of the nucleolus under physiological conditionsNucleoli are non-membrane-bound structures within the nucleus where ribosomal RNA (rRNA) genes are transcribed.These atypical cellular organelles consist of three major compartments with specific functions: (1) fibrillar centers (FC, pre-rRNA synthesis), (2) dense fibrillar components (DFC, pre-RNA processing), and (3) granular components (GC, ribosome assembly). Their organization allows hosting a number of proteins and RNAs with an important role in various cellular processes. Thus the perturbation of nucleolar dynamic assembly exerts profound effects on several cellular functions [1]. A detailed description of nucleolar morphology and organization has been provided elsewhere [1,2]. Here we focus on the mechanisms by which nucleolar activity may regulate neuronal function and survival and contribute especially to neurodegenerative diseases.One intriguing mechanism to control embryonic development, differentiation, and survival is the nucleolar shuttling of cell cycle regulators and transcription factors dictating cell lineage to the nucleoplasm [1]. Moreover, rRNA repression seems required for the execution of differentiation programs. For example, during the embryonic development, transcription of rRNA genes is repressed by lineage-commitment transcription factors turning off the pluripotency genes [3]. During neural lineage commitment there is no direct evidence that rRNA transcription is inhibited; it is likely, however, that mechanisms involving nucleolar dynamics could be in play. For example in brain and retina the levels of the nucleolar protein nucleostemin, a controller of pre-rRNA processing, are rapidly reduced before cell cycle exit and neural differentiation [4,5], suggesting that rRNA biosynthesis may have a regulatory effect on neurogenesis.However, the major regulatory function associated with altered dynamics of nucleolar proteins is connected to the stress response and involv...

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The nucleolar GTP-binding proteins Gnl2 and nucleostemin are required for retinal neurogenesis in developing zebrafish

Cited by 39 publications

References 51 publications

Turning a new page on nucleostemin and self-renewal

Turning a new page on nucleostemin and self-renewal

Cellular and Molecular Preconditions for Retinal Pigment Epithelium (RPE) Natural Reprogramming during Retinal Regeneration in Urodela

Nucleolar activity in neurodegenerative diseases: a missing piece of the puzzle?

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