STANDARD_NAME RASHI_RESPONSE_TO_IONIZING_RADIATION_3 SYSTEMATIC_NAME M7248 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RASHI_RESPONSE_TO_IONIZING_RADIATION_3 NAMESPACE AFFY_MG_U74 DESCRIPTION_BRIEF Cluster 3: genes activated by ionizing radiation regardless of ATM [GeneID=472] status. DESCRIPTION_FULL 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. PMID 16314843 GEOID GSE2118 AUTHORS Rashi-Elkeles S,Elkon R,Weizman N,Linhart C,Amariglio N,Sternberg G,Rechavi G,Barzilai A,Shamir R,Shiloh Y CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Supplementary Table A: cluster 3 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 100307_at,100357_g_at,100413_at,100529_at,100921_at,101325_r_at,101447_at,101843_at,102580_r_at,102673_at,102702_at,103054_at,103760_at,103949_at,104006_at,104158_at,104674_s_at,160880_at,160955_at,161872_f_at,162061_f_at,92209_at,92456_at,92667_at,93086_at,93244_at,93318_at,93463_at,93650_i_at,93708_at,93903_at,94353_at,95001_at,95705_s_at,96264_at,96518_at,96569_at,96577_i_at,97228_at,97340_at,97886_at,98039_at,98296_at,98420_at,99044_at,99329_at,99338_at,99621_s_at,99890_at,99938_at GENE_SYMBOLS NFIX,,YLPM1,UBE2H,TNNI3,FBRS,APC,SH2B1,HOXA6,CREB1,CUEDC1,POLR2A,SETD6,IHH,EPS15,SNW1,PCSK4,MAPK8IP3,FAM136A,,,ULK1,TAF1C,AR,IGKC,TRABD,NINJ1,USP19,PRB1,PIAS3,ACVR2B,EIF4EBP2,AKAP8,ACTB,WDR45B,WWC1,FIGNL1,UBAP2L,ROGDI,SART3,SPR,MICOS13,TULP1,IMPA2,ZNF358,ABCC1,CAND1,SFPQ,PDGFB,XRCC1 FOUNDER_NAMES