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Publication : Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB.

First Author  Croxton R Year  2006
Journal  Cancer Res Volume  66
Issue  18 Pages  9026-35
PubMed ID  16982744 Mgi Jnum  J:112934
Mgi Id  MGI:3664003 Doi  10.1158/0008-5472.CAN-06-1047
Citation  Croxton R, et al. (2006) Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB. Cancer Res 66(18):9026-35
abstractText  Daxx is a nuclear protein that localizes to PML oncogenic domains, sensitizes cells to apoptosis, and functions as a transcriptional repressor. We found that Daxx represses the expression of several antiapoptotic genes regulated by nuclear factor-kappaB, including cIAP2, in human tumor cell lines. Daxx interacts with RelB and inhibits RelB-mediated transcriptional activation of the human cIAP2 gene promoter. Daxx also forms complexes with RelB while bound to its target sites in the cIAP2 promoter, as shown by electrophoretic mobility shift assays and chromatin immunoprecipitation experiments. Using cells from daxx-/- mouse embryos, we observed that levels of the corresponding murine c-IAP mRNA and protein are increased in cells lacking Daxx. Conversely, c-IAP mRNA and protein levels were reduced in relB-/- cells. Taken together, these observations provide a mechanism that links two previously ascribed functions of Daxx: transcriptional repression and sensitization to apoptosis.
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