| 2003 |
NOG1 (GTPBP4) is required for biogenesis of the 60S ribosomal subunit; it co-sediments with 60S ribosomal subunits (not monosomes), co-precipitates 60S precursor RNAs, and localizes to the nucleolus, indicating association with a pre-60S precursor particle. RNAi knockdown dramatically decreases free 60S particles and causes failure to cleave ITS2 from pre-rRNA. Overexpression of a GTP-binding-defective mutant causes a 60S biogenesis defect and reduced processing of large subunit rRNAs. |
Sucrose density gradient sedimentation, RNA co-immunoprecipitation, RNA interference knockdown, dominant-negative overexpression in Trypanosoma brucei |
The Journal of biological chemistry |
High |
12788953
|
| 2006 |
In budding yeast, Nog1 forms a complex with 60S ribosomal proteins and pre-ribosomal proteins Nop7 and Rlp24. The Nog1 complex shuttles between the nucleolus and nucleoplasm for ribosome biogenesis. TOR kinase activity regulates late stages of ribosome maturation by controlling nucleolus-to-nucleoplasm translocation of this complex; nutrient depletion or TOR inactivation tethers the Nog1 complex to the nucleolus, arresting late-stage ribosome biogenesis. Subsequent loss of Nog1 and Nop7 leads to complete cessation of ribosome maturation. |
Co-immunoprecipitation, sucrose gradient sedimentation, rapamycin/nutrient-depletion epistasis, fluorescence localization in Saccharomyces cerevisiae |
The EMBO journal |
High |
16888624
|
| 2007 |
In mouse cells, a point mutation restricting conformational flexibility of the switch II region of Nog1 (GTPBP4) creates a dominant-inhibitory phenotype: the mutant does not significantly affect GTP binding but disrupts productive pre-60S assembly, arrests cell proliferation, impairs processing of multiple pre-rRNA intermediates, causes degradation of nascent 5.8S/28S rRNA precursors, and leads to accumulation of enlarged pre-60S particles in the nucleolus, indicating that switch II conformational changes are critical for dissociation of preribosome-bound factors during intranucleolar maturation. |
Dominant-negative point mutagenesis (switch II region), sedimentation analysis of nucleolar preribosomes, pre-rRNA processing analysis in mouse cells |
Molecular and cellular biology |
High |
17785438
|
| 2007 |
In S. cerevisiae, mutations in conserved GTP-binding pocket residues of Nog1 cause defects in cell growth and 60S ribosome assembly, but mutant proteins retain association with pre-60S particles. Association of Nog1 with pre-60S is independent of guanine nucleotide added to cell extracts. The N-terminal 126 amino acids are required for function; optimal pre-60S association requires sequences between amino acids 347–456. GTP-binding pocket mutations reduce levels of Nog1, Nop2, Nop15, and Tif6 in pre-60S particles. |
Site-directed mutagenesis of GTP-binding motifs, deletion analysis, isobaric labeling mass spectrometry of pre-60S particle composition, sucrose gradient sedimentation in S. cerevisiae |
Molecular genetics and genomics |
High |
17443350
|
| 2020 |
The GTPase Nog1 coordinates assembly, maturation, and quality control of distant ribosomal functional centers on the pre-60S. Drg1-ATPase activity removes Rlp24 from Nog1 on the pre-60S; this extracts the C-terminal tail of Nog1 from the polypeptide exit tunnel (PET), enabling Rei1 to probe PET integrity and catalyze Arx1 release. Concomitantly, Nog1 eviction permits peptidyl transferase center maturation and allows Yvh1 to mediate Mrt4 release for stalk assembly. Thus Nog1 acts as a molecular placeholder coordinating sequential ATPase and GTPase activities during cytoplasmic pre-60S maturation. |
Cryo-EM structural analysis, genetic epistasis, biochemical reconstitution, mass spectrometry of pre-60S particle composition in S. cerevisiae |
eLife |
High |
31909713
|
| 2014 |
In C. elegans, the nog-1 ortholog of GTPBP4 regulates growth, development, lifespan, and fat metabolism. GFP-tagged NOG-1 localizes to the nucleus, while aberrant NOG-1 concentrates in the nucleolus. Knockdown of nog-1 results in smaller brood size, slower growth, increased lifespan, and increased fat storage; overexpression decreases lifespan. Genetic evidence places nog-1 regulation of lifespan and fat storage via the insulin/IGF signaling pathway. |
RNAi knockdown, overexpression, GFP-fusion localization, lifespan and fat storage assays, genetic epistasis with insulin/IGF pathway in C. elegans |
Molecules and cells |
Medium |
24552710
|
| 2018 |
GTPBP4 interacts with p53 in gastric cancer cells, as detected by co-immunoprecipitation. Stable knockdown of GTPBP4 activates p53 and p53-related signaling pathways, inhibits cell proliferation, and promotes apoptosis, placing GTPBP4 upstream of p53 in this cancer context. |
Co-immunoprecipitation, RNA-based high-throughput sequencing, lentiviral stable knockdown, proliferation and apoptosis assays in gastric cancer cells |
Cellular physiology and biochemistry |
Medium |
29408813
|
| 2022 |
GTPBP4 promotes aerobic glycolysis in hepatocellular carcinoma by inducing dimeric PKM2 formation through protein sumoylation. Mechanistically, GTPBP4 facilitates SUMO1 activation by UBA2 and acts as a linker bridging activated SUMO1 and PKM2 to induce PKM2 sumoylation. SUMO-modified PKM2 then translocates from the cytoplasm to the nucleus, contributing to HCC progression via EMT and STAT3 signaling. Promoter methylation by DNMT3A regulates GTPBP4 expression. |
Gain- and loss-of-function studies (in vitro and in vivo), co-immunoprecipitation, protein sumoylation assays, subcellular fractionation, mouse xenograft models |
Redox biology |
Medium |
36116159
|
| 2016 |
GTPBP4 promotes colorectal carcinoma metastasis by disrupting the actin cytoskeleton through repression of RhoA signaling activity, as demonstrated by knockdown (which impedes cell motility) and ectopic overexpression (which enhances cell motility and metastasis). |
Knockdown and ectopic overexpression in colorectal cancer cells, cell motility/invasion assays, RhoA activity measurement |
Biochemical and biophysical research communications |
Low |
27720713
|
| 2023 |
NOG1 (GTPBP4) negatively regulates type I interferon production by interacting with phosphorylated IRF3 and impairing its DNA-binding activity, thereby downregulating IFN-β transcription and downstream ISG expression. NOG1 overexpression inhibits viral RNA- and DNA-mediated IFN signaling; NOG1 deficiency promotes antiviral innate immune responses and resistance to VSV and HSV-1. The GTP-binding domain of NOG1 is required for this function. |
Overexpression and knockout (NOG1-deficient mice), co-immunoprecipitation with phospho-IRF3, DNA-binding activity assay, in vivo viral challenge (VSV, HSV-1), IFN-β ELISA |
PLoS pathogens |
Medium |
37410776
|
| 2025 |
GTPBP4 plays a role in ribosome biogenesis in coronary artery endothelial cells and was identified as a key target gene regulating ribosome biogenesis during myocardial fibrosis progression. Downregulation of GTPBP4 by apigenin suppressed EndMT and alleviated myocardial fibrosis in vitro and in vivo. |
Differential gene screening, knockdown in human coronary artery endothelial cells, in vitro EndMT model (TGF-β1-induced), in vivo animal fibrosis model |
Human cell |
Low |
40938540
|