Human Gene Set: RASHI_RESPONSE_TO_IONIZING_RADIATION_6

For the Mouse gene set with the same name, see RASHI_RESPONSE_TO_IONIZING_RADIATION_6

Standard name RASHI_RESPONSE_TO_IONIZING_RADIATION_6
Systematic name M1560
Brief description Cluster 6: late responding genes activated in ATM [GeneID=472] deficient but not in the wild type tissues.
Full description or abstract The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia, is a master regulator of the cellular network induced by DNA double-strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combined gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation in murine lymphoid tissue. Cluster analysis revealed a prominent pattern characterizing dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of NF-kappaB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and antiapoptotic signals were simultaneously induced, with the proapoptotic pathway mediated by p53 targets, and the prosurvival pathway by NF-kappaB targets. These findings further elucidate the molecular network induced by IR, point to novel putative NF-kappaB targets, and suggest a mechanistic model for cellular balancing between pro- and antiapoptotic signals induced by IR in lymphoid tissues, which has implications for cancer management. The emerging model suggests that restoring the p53-mediated apoptotic arm while blocking the NF-kappaB-mediated prosurvival arm could effectively increase the radiosensitivity of lymphoid tumors.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16314843   Authors: Rashi-Elkeles S,Elkon R,Weizman N,Linhart C,Amariglio N,Sternberg G,Rechavi G,Barzilai A,Shamir R,Shiloh Y
Exact source Supplementary Table A: cluster 6
Related gene sets (show 6 additional gene sets from the source publication)

(show 78 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform or
identifier namespace		 AFFY_MG_U74
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 99 genes
Gene families ? Categorize these 99 genes by gene family
Show members (show 169 source identifiers mapped to 99 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.