Topic
GNL3
About: GNL3 is a research topic. Over the lifetime, 10 publications have been published within this topic receiving 600 citations. The topic is also known as: C77032 & E2IG3.
Papers
TL;DR: A model is proposed that explains how the many contradictory observations surrounding nucleostemin can be reconciled and suggests that this protein might not be as multi-tasking as has been previously perceived.
Abstract: A quintessential trait of stem cells is embedded in their ability to self-renew without incurring DNA damage as a result of genome replication. One key self-renewal factor is the nucleolar GTP-binding protein nucleostemin (also known as guanine-nucleotide-binding 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 card-carrying 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 nucleostemin-depleted 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 multi-tasking 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.
59 citations
TL;DR: It is found that depletion of nucleostemin in a human breast carcinoma cell line triggers prompt and significant DNA damage in S-phase cells without perturbing the initial step of ribosomal (r)RNA synthesis and only mildly affects the total ribosome production.
Abstract: The mammalian nucleolar proteins nucleostemin and GNL3-like (GNL3L) are encoded by paralogous genes that arose from an ancestral invertebrate gene, GNL3. Invertebrate GNL3 has been implicated in ribosome biosynthesis, as has its mammalian descendent, GNL3L. The paralogous mammalian nucleostemin protein has, instead, been implicated in cell renewal. Here, we found that depletion of nucleostemin in a human breast carcinoma cell line triggers prompt and significant DNA damage in S-phase cells without perturbing the initial step of ribosomal (r)RNA synthesis and only mildly affects the total ribosome production. By contrast, GNL3L depletion markedly impairs ribosome production without inducing appreciable DNA damage. These results indicate that, during vertebrate evolution, GNL3L retained the role of the ancestral gene in ribosome biosynthesis, whereas the paralogous nucleostemin acquired a novel genome-protective function. Our results provide a coherent explanation for what had seemed to be contradictory findings about the functions of the invertebrate versus vertebrate genes and are suggestive of how the nucleolus was fine-tuned for a role in genome protection and cell-cycle control as the vertebrates evolved.
42 citations
TL;DR: It is demonstrated that Gnl2 and NS have both non-cell autonomously and cell-autonomous function in correct timing of cell cycle exit and neural differentiation, and the data suggest that Gn l3 and NS affect cell cycleexit of neural progenitors by regulating the expression of cell Cycle regulators independently of p53.
39 citations
1 Jan 2011
TL;DR: In vertebrates, nucleostemin, GNL3L, and Ngp-1 display distinct expression profiles and biological activities that cogently illustrate the complexity of nucleolar biology by showing how this classic organelle integrates a variety of extra- and intra-cellular signals to control key biological events in a dynamic and cell type-specific manner.
Abstract: Nucleostemin, guanine nucleotide binding protein-like 3-like (GNL3L), and Ngp-1 (also known as GNL-2) constitute a novel family of nucleolar GTP-binding proteins that are uniquely defined by the combination of five circularly permuted GTP-binding (G) motifs and nucleolar localization These proteins elegantly reveal the versatility of the nucleolus The most well-known member of this family is nucleostemin, which was first identified as a neural stem cell-enriched gene product and has later become a focus of attention in multiple research areas, including cell cycle regulation, telomere maintenance, stem cell biology, tumorigenesis, and tissue regeneration It has also been used to illustrate the molecular mechanism that controls the dynamic shuttling behavior of nucleolar proteins between the nucleolar and nucleoplasmic compartments New reports have come out that describe not only the biological importance of nucleostemin in mammals but also the functions of its vertebrate paralog, GNL3L, and their common invertebrate ortholog, GNL3 Current data indicate that nucleostemin and GNL3L may have diverged at the inception of vertebrate evolution, and that nucleostemin may have adopted new biological roles while GNL3L inherited the evolutionarily conserved function of GNL3 In vertebrates, nucleostemin, GNL3L, and Ngp-1 display distinct expression profiles and biological activities They cogently illustrate the complexity of nucleolar biology by showing how this classic organelle integrates a variety of extra- and intra-cellular signals to control key biological events in a dynamic and cell type-specific manner
16 citations
TL;DR: Nucleostemin could serve as a powerful prognostic marker for clinical use in osteoarthritis and its usefulness needs to be standardized and validated in a large-scale prospective multicentric study.
11 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2019 | 1 |
| 2018 | 1 |
| 2016 | 1 |
| 2015 | 1 |
| 2014 | 2 |
| 2011 | 2 |