Subcellular Distribution of the Human Putative Nucleolar GTPase GNL1 is Regulated by a Novel Arginine/Lysine-Rich Domain and a GTP Binding Domain in a Cell Cycle-Dependent Manner

Boddapati, Neelima; Anbarasu, K; Suryaraja, R.; Tendulkar, Ashish V.; Mahalingam, Sundarasamy

doi:10.1016/j.jmb.2011.12.066

Cited by 13 publications

(15 citation statements)

References 76 publications

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“…The spatio-temporal requirement for a protein could be decided by the role it has to play at a particular phase of the cell cycle. On a similar note, a nucleolar non-ribosomal protein, GNL-1 is reported to be localized in different cellular compartments in cell cycle dependent manner [ 37 ]. In addition, The Yin-Yang 1 protein (YY1), a ubiquitously expressed zinc-finger transcription factor, accumulates in the nucleus during ‘S’ phase and nuclear export of YY1 is shown to be critical for the inhibition of cellular transformation and tumor growth [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

GNL3L Is a Nucleo-Cytoplasmic Shuttling Protein: Role in Cell Cycle Regulation

et al. 2015

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GNL3L is an evolutionarily conserved high molecular weight GTP binding nucleolar protein belonging to HSR1-MMR1 subfamily of GTPases. The present investigation reveals that GNL3L is a nucleo-cytoplasmic shuttling protein and its export from the nucleus is sensitive to Leptomycin B. Deletion mutagenesis reveals that the C-terminal domain (amino acids 501–582) is necessary and sufficient for the export of GNL3L from the nucleus and the exchange of hydrophobic residues (M567, L570 and 572) within the C-terminal domain impairs this process. Results from the protein-protein interaction analysis indicate that GNL3L interaction with CRM1 is critical for its export from the nucleus. Ectopic expression of GNL3L leads to lesser accumulation of cells in the ‘G2/M’ phase of cell cycle whereas depletion of endogenous GNL3L results in ‘G2/M’ arrest. Interestingly, cell cycle analysis followed by BrdU labeling assay indicates that significantly increased DNA synthesis occurs in cells expressing nuclear export defective mutant (GNL3L∆NES) compared to the wild type or nuclear import defective GNL3L. Furthermore, increased hyperphosphorylation of Rb at Serine 780 and the upregulation of E2F1, cyclins A2 and E1 upon ectopic expression of GNL3L∆NES results in faster ‘S’ phase progression. Collectively, the present study provides evidence that GNL3L is exported from the nucleus in CRM1 dependent manner and the nuclear localization of GNL3L is important to promote ‘S’ phase progression during cell proliferation.

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Section: Discussionmentioning

confidence: 99%

GNL3L Is a Nucleo-Cytoplasmic Shuttling Protein: Role in Cell Cycle Regulation

et al. 2015

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“…It encodes 607 amino acids with a molecular mass of 65 kDa and contains basic amino acids rich N-terminus, acidic amino acids rich C-terminus and proline rich-domains. Previous report from our laboratory provided evidence that GNL1 harbors a novel arginine/lysine-rich nuclear/nucleolar localization signal and localized in different subcellular compartments in cell cycle dependent manner 10 . The presence of GTP binding motifs indicate that GNL1 can acts as molecular switch to control its transition between nucleus and cytoplasm (10).…”

Section: Introductionmentioning

confidence: 88%

Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation

Krishnan

Boddapati

Mahalingam

2018

Sci Rep

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Human Guanine nucleotide binding protein like 1 (GNL1) belongs to HSR1_MMR1 subfamily of nucleolar GTPases. Here, we report for the first time that GNL1 promotes cell cycle and proliferation by inducing hyperphosphorylation of retinoblastoma protein. Using yeast two-hybrid screening, Ribosomal protein S20 (RPS20) was identified as a functional interacting partner of GNL1. Results from GST pull-down and co-immunoprecipitation assays confirmed that interaction between GNL1 and RPS20 was specific. Further, GNL1 induced cell proliferation was altered upon knockdown of RPS20 suggesting its critical role in GNL1 function. Interestingly, cell proliferation was significantly impaired upon expression of RPS20 interaction deficient GNL1 mutant suggest that GNL1 interaction with RPS20 is critical for cell growth. Finally, the inverse correlation of GNL1 and RPS20 expression in primary colon and gastric cancers with patient survival strengthen their critical importance during tumorigenesis. Collectively, our data provided evidence that cross-talk between GNL1 and RPS20 is critical to promote cell proliferation.

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“…Its subcellular location is similar to Gnl1, another YRG protein which is localized mainly in the cytosol while shuttling to nucleus and nucleolus in the cell cycle stage G2 [32]. Finally, three proteins are restricted to the nuclear compartment and intra subcompartments: Gnl2, present in all of the eukaryotic proteomes and shuttling between nucleus and nucleolus [33]; Gnl3l, absent in some Alveolata proteomes and specific to the nucleolus [34], and Gnl3, also known as Nucleostemin, only present in Chordata [35].…”

Section: Resultsmentioning

confidence: 99%

“…The fact that it shuttles both to nucleus and nucleolus [32] suggests its evolution related to the increase in complexity of the nuclear compartment. While the most parsimonious explanation for the evolution of Gnl1 is that it emerged as a duplication of Lsg1 in the metazoan lineage (Fig 3), our phylogeny does not support this as the Gnl1 subfamily clusters outside Lsg1 suggesting that it was lost in Fungi and Viridiplantae.…”

Section: Resultsmentioning

confidence: 99%

Reading the Evolution of Compartmentalization in the Ribosome Assembly Toolbox: The YRG Protein Family

et al. 2017

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Reconstructing the transition from a single compartment bacterium to a highly compartmentalized eukaryotic cell is one of the most studied problems of evolutionary cell biology. However, timing and details of the establishment of compartmentalization are unclear and difficult to assess. Here, we propose the use of molecular markers specific to cellular compartments to set up a framework to advance the understanding of this complex intracellular process. Specifically, we use a protein family related to ribosome biogenesis, YRG (YlqF related GTPases), whose evolution is linked to the establishment of cellular compartments, leveraging the current genomic data. We analyzed orthologous proteins of the YRG family in a set of 171 proteomes for a total of 370 proteins. We identified ten YRG protein subfamilies that can be associated to six subcellular compartments (nuclear bodies, nucleolus, nucleus, cytosol, mitochondria, and chloroplast), and which were found in archaeal, bacterial and eukaryotic proteomes. Our analysis reveals organism streamlining related events in specific taxonomic groups such as Fungi. We conclude that the YRG family could be used as a compartmentalization marker, which could help to trace the evolutionary path relating cellular compartments with ribosome biogenesis.

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Subcellular Distribution of the Human Putative Nucleolar GTPase GNL1 is Regulated by a Novel Arginine/Lysine-Rich Domain and a GTP Binding Domain in a Cell Cycle-Dependent Manner

Cited by 13 publications

References 76 publications

GNL3L Is a Nucleo-Cytoplasmic Shuttling Protein: Role in Cell Cycle Regulation

GNL3L Is a Nucleo-Cytoplasmic Shuttling Protein: Role in Cell Cycle Regulation

Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation

Reading the Evolution of Compartmentalization in the Ribosome Assembly Toolbox: The YRG Protein Family

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