Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling
Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling
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DOI：
10.1074/jbc.m305171200
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发表时间：
2003-11-28
影响因子：
4.8
通讯作者：
Chellappan, S
中科院分区：
文献类型：
--
作者：
Fusaro, G;Dasgupta, P;Chellappan, S
Prohibitin是一种潜在的肿瘤抑制蛋白，具有抑制细胞增殖和抑制E2 F转录活性的作用。虽然prohibitin在细胞核中具有强大的转录功能，但也有人提出了prohibitin在线粒体中的作用。在这里，我们表明，prohibitin主要是核在两个乳腺癌细胞系，它与E2 F1和p53共定位。在喜树碱的凋亡刺激下，抑制素被输出到核周区域，在那里它定位于线粒体。这里提供的数据还表明，抑制素能够在体内和体外与p53物理相互作用。Prohibitin被发现增强p53介导的转录活性，并且反义Prohibitin构建体的共转染降低了p53介导的转录激活。抑制蛋白似乎诱导p53介导的转录，通过增强其募集启动子，检测染色质免疫沉淀试验。这些结果表明，prohibitin能够调节Rb/E2 F以及p53调节途径。
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.