Systematic name M1897
Brief description Cluster 1: ATM [GeneID=472] dependent genes induced at 30 min after ionizing radiation treatment.
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 gene sets
      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 1
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(show 78 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_MG_U74
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Version history 3.0: First introduced

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