Similar Datasets
Project description:The regulation of replication forks stalling and replication origins firing must be tightly coordinated to prevents genomic instability. Here we show that GNL3/nucleostemin, a GTP-binding protein able to shuttle between the nucleolus and the nucleoplasm, limits replicative stress by limiting replication origins firing. GNL3 is in proximity of nascent DNA and its depletion reduces forks speed but increases forks density and replication origins firing. When subjected to exogenous replicative stress, cells impaired for GNL3 exhibits MRN-dependent resection and RPA phosphorylation. Strikingly, inhibition of origin firing using CDC7 inhibitor decreased resection in absence of GNL3 but not in absence of BRCA1, suggesting that GNL3 does not protect nascent strand directly from resection. Consistent with this, overexpression of GNL3 leads to an increased resection in response to replicative stress and enhanced origin firing efficiency. These data indicate that the probability of origins firing is tightly regulated by GNL3 to limit replicative stress. Finally, we show that ORC2 and GNL3 interacts together in the nucleolus. We propose a model where GNL3 level is crucial to determine the correct amount of ORC2 on chromatin by sequestrating it in the nucleolus thanks to the capacity of GNL3 to shuttle between nucleoplasm and nucleolus.
2023-07-01 | GSE180865 | GEO
Project description:Androgen receptor (AR) signaling is a primary oncogenic driver of castration-resistant prostate cancer (CRPC), yet the mechanism remains incompletely understood. Through proteomic profiling of CRPC and primary PCa cells, we identify G Protein Nucleolar 3 (GNL3) as a novel AR coregulator. GNL3 physically interacts with AR, enhances its chromatin occupancy, and directly coactivates transcriptional programs that promote cell proliferation, including NEK2 and CDC20. Concurrently, GNL3 functions as a corepressor of immune-responsive genes such as CXCL10 and TAP1 via class I histone deacetylases (HDACs), thereby facilitating CD8+ T cell elimination and establishing an immunosuppressive tumor microenvironment. GNL3 expression and AR-GNL3 complex formation progressively increase from normal prostate to CRPC and correlate with poor clinical outcomes. Functionally, GNL3 knockdown sensitizes CRPC cells to AR antagonists and impairs tumor growth and metastasis. Furthermore, we demonstrate that combinatorial inhibition of NEK2, class I HDACs, and AR signaling can be a potential therapeutic strategy for CRPC. Overall, these findings establish GNL3 as a dual-function AR coregulator and therapeutic target, providing mechanistic insights into transcriptional regulation and immune evasion in advanced PCa.
2026-05-13 | GSE305109 | GEO
Project description:BAF170 ChIP-chip performed on Human Hela S3 Cells for Nimblegen ENCODE arrays which comprise 50mer oligonucleotides spaced every 38bps (overlapping by 12nts). Goal is to identify binding sites for BAF170. Keywords = Transcription Factor Binding, BAF170, ChIP-chip, Human, Genome Tiling Arrays Keywords: ChIP-chip
2005-11-04 | GSE3550 | GEO
Project description:BAF155 ChIP-chip performed on Human Hela S3 Cells for Nimblegen ENCODE arrays which comprise 50mer oligonucleotides spaced every 38bps (overlapping by 12nts). Goal is to identify binding sites for BAF155. Keywords = Transcription Factor Binding, BAF155, ChIP-chip, Human, Genome Tiling Arrays Keywords: ChIP-chip
2005-11-04 | GSE3549 | GEO
Project description:JUN ChIP-chip performed on Human Hela S3 Cells for Nimblegen ENCODE arrays which comprise 50mer oligonucleotides spaced every 38bps (overlapping by 12nts). Goal is to identify binding sites for JUN. Keywords = Transcription Factor Binding, JUN, ChIP-chip, Human, Genome Tiling Arrays Keywords: ChIP-chip
2005-10-19 | GSE3448 | GEO
Project description:FOS ChIP-chip performed on Human Hela S3 Cells for Nimblegen ENCODE arrays which comprise 50mer oligonucleotides spaces every 38bps (overlapping by 12nts). Goal was to identify FOS-binding sites. Keywords = Transcription Factor Binding, FOS, ChIP-chip, Human, Genome Tiling Arrays Keywords: ChIP-chip
2005-10-19 | GSE3449 | GEO
Project description:TAF II p250 ChIP-chip performed on Human Hela S3 Cells for Nimblegen ENCODE arrays which comprise 50mer oligonucleotides spaces every 38bps (overlapping by 12nts). Goal was to identify TAF II p250-binding sites. Keywords = Transcription Factor Binding, TAF II p250, ChIP-chip, Human, Genome Tiling Arrays Keywords: ChIP-chip
2005-10-19 | GSE3450 | GEO
Project description:We used two siRNAs to knock down GNL3 in human neural progenitor cells which were derived from normal human induced pluripotent stem cells (ATCC, ACS-1011). GNL3 knockdown experiments were done in three biological replicates. Total RNA was extracted from GNL3 knockdown and control groups for RNA sequencing (Illumina Hiseq2000, paired-end 100 bp). Genes that affected by both siRNAs were considered differentially expressed genes between GNL3 knockdown and control groups (adjusted P value < 0.05). Using Gene Ontology and KEGG pathway analysis, we found that those differentially exrepssed genes were mainly related to immune response, response to cytokine, cell cycle, and p53 signaling pathway.
2020-05-21 | GSE150945 | GEO
Project description:Androgen receptor (AR) signaling is a primary oncogenic driver of castration-resistant prostate cancer (CRPC), yet the mechanism remains incompletely understood. Through proteomic profiling of CRPC and primary PCa cells, we identify G Protein Nucleolar 3 (GNL3) as a novel AR coregulator. GNL3 physically interacts with AR, enhances its chromatin occupancy, and directly coactivates transcriptional programs that promote cell proliferation, including NEK2 and CDC20. Concurrently, GNL3 functions as a corepressor of immune-responsive genes such as CXCL10 and TAP1 via class I histone deacetylases (HDACs), thereby facilitating CD8+ T cell elimination and establishing an immunosuppressive tumor microenvironment. GNL3 expression and AR-GNL3 complex formation progressively increase from normal prostate to CRPC and correlate with poor clinical outcomes. Functionally, GNL3 knockdown sensitizes CRPC cells to AR antagonists and impairs tumor growth and metastasis. Furthermore, we demonstrate that combinatorial inhibition of NEK2, class I HDACs, and AR signaling can be a potential therapeutic strategy for CRPC. Overall, these findings establish GNL3 as a dual-function AR coregulator and therapeutic target, providing mechanistic insights into transcriptional regulation and immune evasion in advanced PCa.
2026-05-13 | GSE305110 | GEO