CEA_SGF:E00002#REtsAF-Bcl2_ZVAD
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE1109 | GEO | 2004/06/01
SECONDARY ACCESSION(S): PRJNA87213
REPOSITORIES: GEO
Similar Datasets
Project description:p53 can induce apoptosis through multiple mechanisms including transactivation, transrepression or protein interactions but the determinism of the choice between them is poorly understood. In order to know the role of caspases in this choice, effect of caspase inhibition by ZVAD on p53 target genes transcription is tested by DNA chip analysis.
2004-06-01 | E-GEOD-1109 | biostudies-arrayexpress
Project description:Certain Inhibitors of apoptosis (IAP) family members are sentinel proteins preventing untimely cell death by inhibiting caspases. Antagonists including second mitochondria-derived activator of caspase (SMAC) regulate IAPs, driving cell death. Baculoviral IAP repeat-containing protein 6 (BIRC6), a giant IAP with dual E2/E3 ubiquitin ligase activity, regulates programmed cell death through unknown mechanisms. We show BIRC6 directly restricts executioner caspases-3 and -7, and ubiquitinates caspases-3, -7 and -9 working exclusively with non canonical E1, UBA6. Importantly, we show SMAC supresses both mechanisms. Cryo-electron microscopy structures of BIRC6 alone and in complex with SMAC reveals BIRC6 is an anti parallel dimer juxtaposing the substrate-binding module against the catalytic domain. Furthermore, we discover SMAC multi-site binding to BIRC6 results in a sub-nanomolar affinity interaction, enabling SMAC to competitively displace caspases thus antagonising BIRC6 anti-caspase function.
2023-03-08 | PXD039954 | Pride
Project description:Targeting “oncogene addiction” is a promising strategy for anti-cancer therapy. Here, we report a potent inhibition of crucial oncogenes by p53 upon reactivation with small molecule RITA in vitro and in vivo. RITA-activated p53 unleashes transcriptional repression of anti-apoptotic proteins Mcl-1, Bcl-2, MAP4, and survivin, blocks Akt pathway on several levels and downregulates c-Myc, cyclin E and B-catenin. p53 ablates c-Myc expression via several mechanisms at transcriptional and posttranscriptional level. We show that transrepression of oncogenes correlated with higher level of p53 bound to chromatin-bound p53 than transactivation of pro-apoptotic targets. Inhibition of oncogenes by p53 reduces the cell’s ability to buffer pro-apoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression. Experiment Overall Design: Breast carcinoma cell-line MCF7 was treated with the small-molecule p53 activator RITA for 2h, 8h, 16h and 24h.
2009-05-15 | E-GEOD-13291 | biostudies-arrayexpress
Project description:Targeting “oncogene addiction” is a promising strategy for anti-cancer therapy. Here, we report a potent inhibition of crucial oncogenes by p53 upon reactivation with small molecule RITA in vitro and in vivo. RITA-activated p53 unleashes transcriptional repression of anti-apoptotic proteins Mcl-1, Bcl-2, MAP4, and survivin, blocks Akt pathway on several levels and downregulates c-Myc, cyclin E and B-catenin. p53 ablates c-Myc expression via several mechanisms at transcriptional and posttranscriptional level. We show that transrepression of oncogenes correlated with higher level of p53 bound to chromatin-bound p53 than transactivation of pro-apoptotic targets. Inhibition of oncogenes by p53 reduces the cell’s ability to buffer pro-apoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression. Keywords: time course
2009-05-12 | GSE13291 | GEO
Project description:The project is directed to the development of selective glucocorticoid receptor agonists for anticancer therapy. Glucocorticoids (GC) are widely used in treatment of many types of cancer due to its ability to induce apoptosis in malignant cells (in blood cancer therapy) and to prevent nausea and emesis (in the chemotherapy of solid tumors). However, severe dose-limiting side effects occur, including osteoporosis, muscle wasting, diabetes and other metabolic complications. Both beneficial and harmful effects of glucocorticoids are due to selective activation or repression of particular genes by glucocorticoid receptor (GR). GR regulates gene expression via transactivation that requires GR homodimer binding to gene promoters and transrepression mediated via negative interaction between GR and other transcription factors as well as binding with negative glucocorticoid response elements (nGRE) in genes. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. Novel selective GR agonist Compound A (CpdA) prevents GR dimerization and transactivation, specifically activates GR transrepression, and has fewer side effects compared to glucocorticoids. Here we compare the gene expression profiles in prostate cancer cells treated with glucocorticoid Dexamethasone (Dex) or CpdA
2015-07-21 | GSE71099 | GEO
Project description:The project is directed to the development of selective glucocorticoid receptor agonists for anticancer therapy. Glucocorticoids (GC) are widely used in treatment of many types of cancer due to its ability to induce apoptosis in malignant cells (in blood cancer therapy) and to prevent nausea and emesis (in the chemotherapy of solid tumors). However, severe dose-limiting side effects occur, including osteoporosis, muscle wasting, diabetes and other metabolic complications. Both beneficial and harmful effects of glucocorticoids are due to selective activation or repression of particular genes by glucocorticoid receptor (GR). GR regulates gene expression via transactivation that requires GR homodimer binding to gene promoters and transrepression mediated via negative interaction between GR and other transcription factors as well as binding with negative glucocorticoid response elements (nGRE) in genes. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. Novel selective GR agonist Compound A (CpdA) prevents GR dimerization and transactivation, specifically activates GR transrepression, and has fewer side effects compared to glucocorticoids. Here we compare the gene expression profiles in lymphoma cells treated with glucocorticoid Dexamethasone (Dex) or CpdA
2015-07-21 | GSE71102 | GEO
Project description:The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago, however its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provides a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell fate decisions, and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice.
2016-08-18 | GSE84986 | GEO
Project description:Caspases are cysteine-proteases with key roles in the execution phase of apoptosis. Additional cellular activities, unrelated to cell death seem to be influenced by these enzymes. Identification of genes co-regulated with caspases could help to ascertain new biological roles for these proteases.To identify genes and pathways under the influence of caspase-2 we silenced its expression in U87MG glioblastoma cell line. Transcriptional expression profiles of cells transfected with caspase-2 siRNA or control siRNA were compared.
2014-09-13 | GSE61388 | GEO
Project description:Caspases are cysteine-proteases with key roles in the execution phase of apoptosis. Additional cellular activities, unrelated to cell death seem to be influenced by these enzymes. Identification of genes co-regulated with caspases could help to ascertain new biological roles for these proteases.To identify genes and pathways under the influence of caspase-2 we silenced its expression in U87MG glioblastoma cell line. Transcriptional expression profiles of cells transfected with caspase-2 siRNA or control siRNA were compared. Gene expression profiling was evaluated from 2 replicates of U87MG cells transfected with CASP2-siRNA, or with Control-siRNA.
2014-09-13 | E-GEOD-61388 | biostudies-arrayexpress
Project description:Characterization of the transcriptional profile of SP human keratinocytes from primary cultures. Keywords: repeat sample
2005-10-01 | GSE2467 | GEO