Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling

被引:277
作者
Fusaro, G
Dasgupta, P
Rastogi, S
Joshi, B
Chellappan, S [1 ]
机构
[1] Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA
[2] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
关键词
D O I
10.1074/jbc.M305171200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Prohibitin, a potential tumor suppressor protein, has been shown to inhibit cell proliferation and repress E2F transcriptional activity. Though prohibitin has potent transcriptional functions in the nucleus, a mitochondrial role for prohibitin has also been proposed. Here we show that prohibitin is predominantly nuclear in two breast cancer cell lines where it co-localizes with E2F1 and p53. Upon apoptotic stimulation by camptothecin, prohibitin is exported to perinuclear regions where it localizes to mitochondria. The data presented here also show that prohibitin is capable of physically interacting with p53 in vivo and in vitro. Prohibitin was found to enhance p53-mediated transcriptional activity and cotransfection of an antisense prohibitin construct reduces p53-mediated transcriptional activation. Prohibitin appears to induce p53-mediated transcription by enhancing its recruitment to promoters, as detected by chromatin immunoprecipitation assays. These results suggest that prohibitin is capable of modulating Rb/E2F as well as p53 regulatory pathways.
引用
收藏
页码:47853 / 47861
页数:9
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