STANDARD_NAME RASHI_RESPONSE_TO_IONIZING_RADIATION_6 SYSTEMATIC_NAME M1560 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/RASHI_RESPONSE_TO_IONIZING_RADIATION_6 NAMESPACE AFFY_MG_U74 DESCRIPTION_BRIEF Cluster 6: late responding genes activated in ATM [GeneID=472] deficient but not in the wild type tissues. 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 6 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 100012_at,100037_at,100295_at,100299_f_at,100322_at,100360_f_at,100362_f_at,100376_f_at,100377_f_at,100397_at,100489_at,100682_f_at,100721_f_at,100981_at,101048_at,101144_at,101157_at,101298_g_at,101319_f_at,101320_f_at,101326_at,101330_f_at,101331_f_at,101347_at,101395_at,101436_at,101468_at,101616_at,101633_at,101640_f_at,101656_f_at,101718_f_at,101720_f_at,101743_f_at,101745_f_at,101747_f_at,101751_f_at,101752_f_at,101753_s_at,101764_at,101865_at,101870_at,101871_f_at,102025_at,102076_at,102154_f_at,102155_f_at,102156_f_at,102157_f_at,102264_at,102293_at,102337_s_at,102382_at,102553_at,102585_f_at,102712_at,102721_at,102722_g_at,102794_at,102823_at,102824_g_at,102843_s_at,102978_at,103089_at,103221_at,103231_at,103375_at,103448_at,103488_at,103631_at,103763_at,103887_at,103913_at,104270_at,104286_at,104388_at,104468_at,104666_at,160090_f_at,160266_r_at,160355_at,160382_at,160546_at,160627_at,160757_at,160768_at,160781_r_at,160815_at,160862_at,160934_s_at,161012_at,161437_f_at,161650_at,161689_f_at,161832_r_at,161881_f_at,161946_r_at,162026_r_at,162037_f_at,92315_at,92316_f_at,92459_at,92470_f_at,92482_at,92715_at,92858_at,93085_at,93213_at,93227_f_at,93234_at,93365_s_at,93397_at,93583_s_at,93593_f_at,93676_at,93831_at,93837_at,93904_f_at,93912_at,93927_f_at,94542_at,94725_f_at,94829_at,94906_at,95152_g_at,95303_at,95806_f_at,95861_at,95974_at,96232_at,96598_at,96729_at,96963_s_at,96964_at,96970_at,96971_f_at,96972_f_at,96973_f_at,96974_at,96975_at,96992_r_at,97008_f_at,97009_f_at,97441_at,97563_f_at,97564_f_at,97566_f_at,97567_f_at,97574_f_at,97575_f_at,97576_f_at,97577_f_at,98025_at,98041_at,98406_at,98408_at,98761_i_at,98765_f_at,98951_at,99185_at,99330_at,99366_at,99369_f_at,99405_at,99446_at,AFFX-BioB-5_at,AFFX-BioB-M_at,AFFX-CreX-3_at,AFFX-MurFAS_at GENE_SYMBOLS LAPTM5,DDX18,IGLV4-69,IGKV1D-43,,IGHV1-58,IGHV1-58,IGHV1-58,IGHV1-69-2,TYROBP,PDE7A,,IGHV1-58,IFIT1B,PTPRC,IL18R1,,PTPRC,,,IGHV2-26,,IGKV4-1,,,CXCL9,CFP,IGKV1-37,IGKV5-2,,,,IGKV4-1,,,,,,LYZ,HTR1D,PIP4K2A,IGHG1,,CXCL13,,IGKV4-1,,,,,IKZF1,FCGR2B,BMAL1,,,SAA3P,,,CXCR4,IGHG1,IGHG1,,MIR142,CD48,SAAL1,RHOH,ZCCHC3,S100A8,SELPLG,ZNF688,ASH1L,S100A9,SEC61A2,GRK2,SLC38A4,CCL15,INCENP,ZNF653,ALDOA,BRIX1,MAZ,RRP7A,ALDOC,DDX52,RNF38,C9orf40,UNC93B1,FERMT3,PTP4A3,,CD79B,,,IL1R2,,,,,,SLFN12L,IGLC1,CCL8,IGHV1-58,FMNL1,UBD,SLPI,PSMB9,IGKV1D-43,IGKV4-1,MSC,SUGT1,CCR2,IGHM,EMP3,RAD51AP1,NONO,KNG1,IGHV1-69-2,BAG6,IGHV1-69-2,MBTD1,,TMEM70,ADH1C,PLEKHO1,,,,GBP2,CUL2,CCNJ,EIF4EBP2,IGKV4-1,,,,,IGHV1-45,IGKV1D-33,,,IGHV1-69-2,IGHV1-69-2,ACIN1,IGHV1-58,,,,IGHV1-58,,,,EVI2A,RNASE1,CCL5,HHEX,,IGHV3-66,TCF25,MRPL41,CSF2RA,SLC66A3,,IGKV2D-30,MS4A1,,,,FAS FOUNDER_NAMES