Daxx represses expression of a subset of antiapoptotic genes regulated by nuclear factor-κB

被引：42

作者：

Croxton, Rhonda ^{[1
]}

Puto, Lorena A. ^{[1
]}

de Belle, Ian ^{[1
]}

Thomas, Michael ^{[1
]}

Torii, Seiji ^{[1
]}

Hanaii, Farid ^{[1
]}

Cuddy, Michael ^{[1
]}

Reed, John C. ^{[1
]}

机构：

[1] Burnham Inst Med Res, La Jolla, CA 92037 USA

来源：

CANCER RESEARCH | 2006年 / 66卷 / 18期

关键词：

D O I：

10.1158/0008-5472.CAN-06-1047

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-kappa B, including cIAP2, in human tumor cell lines. Daxx interacts with ROB and inhibits RelB-mediated transcriptional activation of the human cIAP2 gene promoter. Daxx also forms complexes with ROB. 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-LAP mRNA and protein are increased in cells lacking Daxx. Conversely, c-LAP 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.

引用

页码：9026 / 9035

页数：10

共 39 条

[1] Active repression of antiapoptotic gene expression by ReIA(p65) NF-κB [J].