Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of Hsp70 inhibitor JG-98 on gene expression in mouse macrophages

ABSTRACT: JG-98 reduces migration of macrophages. We assessed how this compound affects expression of genes associated with motility and migration. A number of motility/migration genes were significantly downregulated.

ORGANISM(S): Mus musculus

PROVIDER: GSE82311 | GEO | 2016/12/19

SECONDARY ACCESSION(S): PRJNA324600

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Effect of the Hsp70 inhibitor JG-98 on gene expression in MCF7 cells

Project description:Hsp70 inhibition affects many signaling pathways. We established how these effects are translated into changes in gene expression. Hsp70 is a promising anti-cancer target, and several inhibitors of Hsp70 have been recently developed. Interest to Hsp70 inhibitors as drug prototypes is, however, somewhat hampered by potential similarity of their physiological effects to effects of already well-developed Hsp90 inhibitors. JG-98 series of inhibitors is unique in its ability to target an allosteric site in the ATPase domain of Hsp70, which disrupts its interaction with a co-chaperone Bag3 and affects a variety of signaling pathways important for cancer development and survival. Here, we used the Broad Institute Connectivity Map platform to evaluate physiological effects of JG-98, and found that these effects are dissimilar from effects of Hsp90 inhibitors, thus justifying further development of this compound series. Further, using gene expression data and ActivSignal IPAD platform, we identified pathways modulated by JG-98. Some of these pathways were affected by JG-98 in Bag3-dependent and some pathways in Bag3-independent manner, indicating multiple mechanisms of JG-98 action. Using pooled shRNA genetic screen, we established gene sets that modulate the response of cancer cells to JG-98. Based on genetic and gene expression information, we developed approaches to predict potent combinations of JG-98 with known drugs. These predictions were validated by demonstrating that proteasome, RNApol II, Akt and RTK inhibitors synergize with anti-cancer effects of JG-98. Overall, in this study we analyze unique effects of Hsp70 inhibitors of JG-98 series on cell physiology and define potential drug combinations for clinical use of these inhibitors.

2018-01-11 | GSE93542 | GEO

A2780 and OVCAR-3 Cells:Control vs. LS-98 treated

2011-06-01 | GSE29668 | GEO

Cytoplasmic proteotoxicity regulates HRI-dependent phosphorylation of eIF2a via the Hsp70-Bag3 module.

Project description:The major heat shock protein Hsp70 has been shown to form a complex with a scaffold protein Bag3, linking it to multiple signaling pathways. Via these interactions, the Hsp70-Bag3 module functions as a proteotoxicity sensor that controls cell signaling. Here, as a tool to identify signaling pathways regulated by this complex, we utilized JG-98, an allosteric inhibitor of Hsp70 that blocks its interaction with Bag3. Gene expression profiling followed by the pathway analysis indicated that a set of signaling pathways including the unfolded protein response (UPR) was activated by JG-98. Surprisingly, only the translation initiation factor eIF2a-associated branch of the UPR was activated under these conditions, while other UPR branches mediating induction of ER chaperones were not induced, suggesting that the response was not related to ER proteotoxicity and thus to ER-associated kinase PERK1. Indeed, induction of the UPR genes under these conditions was dependent on activation of a distinct cytoplasmic eIF2a kinase, HRI. We demonstrated that the Hsp70-Bag3 complex directly interacted with HRI and regulated phosphorylation of eIF2a upon induction of cytoplasmic proteotoxicity. Therefore, we uncovered a novel signaling response, which regulates cell death upon the buildup of abnormal protein species in cytoplasm via an Hsp70-Bag3-HRI-eIF2a axis.

2021-04-14 | GSE171440 | GEO

A2780 and OVCAR-3 Cells:Control vs. LS-98 treated

Project description:Transcriptional profiling of human ovarian cancer cells comparing control vehicle-treated A2780 and OVCAR-3 (Human ovarian cancer cell lines) cells with A2780 and OVCAR-3 cells treated with 5μM LS-98 for 24 hours.Goal was to determine the effects of LS-98 compound on the global A2780 and OVCAR-3 cells gene expression. One-condition experiment, control vehicle-treated A2780 and OVCAR-3 vs. LS098 treated-A2780 and OVCAR-3 cells. Biological replicates: 2 replicates.

2011-06-01 | E-GEOD-29668 | biostudies-arrayexpress

Mitoribosome sensitivity to HSP70 inhibition uncovers metabolic liabilities of castration-resistant prostate cancer

Project description:TMT-MS of whole cell lysate collected from 22Rv1 castration-resistant prostate cancer cells treated with 5 µM JG-98 for 4 hours.

2023-04-25 | PXD038684 | JPOST Repository