| First Author | Rashi-Elkeles S | Year | 2006 |
| Journal | Oncogene | Volume | 25 |
| Issue | 10 | Pages | 1584-92 |
| PubMed ID | 16314843 | Mgi Jnum | J:107288 |
| Mgi Id | MGI:3620502 | Doi | 10.1038/sj.onc.1209189 |
| Citation | Rashi-Elkeles S, et al. (2006) Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue. Oncogene 25(10):1584-92 |
| abstractText | 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. |
