Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-kappaB.
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.
Croxton
Rhonda
R
Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Puto
Lorena A
LA
de Belle
Ian
I
Thomas
Michael
M
Torii
Seiji
S
Hanaii
Farid
F
Cuddy
Michael
M
Reed
John C
JC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D018832:Molecular Chaperones; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051841:Transcription Factor RelB / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D051034:Inhibitor of Apoptosis Proteins; D018832:Molecular Chaperones; D016328:NF-kappa B; D009687:Nuclear Proteins; D051841:Transcription Factor RelB