共查询到20条相似文献,搜索用时 657 毫秒
1.
2.
3.
4.
5.
6.
7.
《Cell cycle (Georgetown, Tex.)》2013,12(9):1133-1138
Upon treatment with some DNA damaging agents, human H1299 tumor-derived cells expressing inducible versions of wild-type or mutant p53 with inactive transactivation domain I (p53Q22/S23) undergo apoptosis. In cells expressing either version of p53, caspase 2 activation is required for release of cytochrome c and cell death. Furthermore, silencing of PIDD (a factor previously shown to be required for caspase 2 activation) by siRNA suppresses apoptosis by both wild-type p53 and p53Q22/S23. Despite the finding that caspase 2 is essential for DNA damage-facilitated, p53-mediated apoptosis, induction of wild-type p53 (with or without DNA damage) resulted in a reduction of caspase 2 mRNA and protein levels. In this study we sought to provide a mechanism for the negative regulation of caspase 2 by p53 as well as provide insight as to why p53 may repress a key mediator of p53-dependent apoptosis. Mechanistically, we show that DNA binding and/or transactivation domains of p53 are crucial for mediating transrepression. Further, expression of p21 (in p53-null cells inducibly expressing p21) is sufficient to mediate repression of caspase 2. Deletion of p21 or E2F-1 not only abrogated repression of caspase 2, but also stimulated the expression of caspase 2 above basal levels, implicating the requirement for an intact p21/Rb/E2F pathway in the down-regulation of caspase 2. As this p53/p21-dependent repression of caspase 2 can occur in the absence of DNA damage, caspase 2 repression does not simply seem to be a consequence of the apoptotic process. Down-regulation of caspase 2 levels by p53 may help to determine cell fate by preventing cell death when unnecessary. 相似文献
8.
S Kubicka F Kühnel L Zender K L Rudolph J Plümpe M Manns C Trautwein 《The Journal of biological chemistry》1999,274(45):32137-32144
9.
10.
11.
12.
TIP60 represses transcriptional activity of p73beta via an MDM2-bridged ternary complex 总被引:1,自引:0,他引:1
Kim JW Song PI Jeong MH An JH Lee SY Jang SM Song KH Armstrong CA Choi KH 《The Journal of biological chemistry》2008,283(29):20077-20086
13.
14.
Transcriptional activation of p53 by Pitx1 总被引:1,自引:0,他引:1
15.
16.
17.
18.
19.