Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites
Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites
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DOI：
10.1042/bj20060364
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发表时间：
2007-01-01
影响因子：
4.1
通讯作者：
Chellappan, S. P.
中科院分区：
文献类型：
--
作者：
Joshi, B.;Rastogi, S.;Chellappan, S. P.
抑制素是一种30 kDa的生长抑制蛋白，在细胞中具有多效性功能。虽然抑制素已被证明具有有效的转录调节功能，它也被提出，以促进蛋白质折叠在线粒体和促进细胞迁移与Raf-1。我们之前的研究表明，抑制素与E2 F家族成员的标记盒结构域发生物理相互作用，并抑制其转录活性;相比之下，抑制素可以结合并增强p53的转录活性。在这里，我们表明，人类YY 1（阴阳1），以及caspase 7基因的启动子抑制素调制。YY 1启动子活性降低过表达的prohibitin，而当prohibitin被小干扰RNA技术耗尽时，它被增强。通过突变分析和染色质免疫沉淀试验，发现抑制素对YY 1启动子的抑制作用通过E2 F结合位点介导。此外，E2 F1的耗竭阻止了prohibitin抑制YY 1启动子。与YY 1相反，probibitin过度表达导致caspase 7水平的提高，而prohibitin的耗尽降低了它。有趣的是，caspase 7启动子被发现有p53结合位点和prohibitin激活这个启动子通过p53。这些研究表明，prohibitin对不同基因的表达具有不同的影响，并且各种细胞启动子的活性受到prohibitin的影响。此外，它似乎很可能是通过影响不同英亩的转录抑制素进行其许多细胞功能。
Prohibitin is a 30 kDa growth suppressive protein that has pleiotropic functions in the cell. Although prohibitin has been demonstrated to have potent transcriptional regulatory functions, it has also been proposed to facilitate protein folding in the mitochondria and promote cell migration in association with Raf-1. Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53. Here, we show that promoters of human YY1 (Yin and Yang 1) as well as caspase 7 genes are modulated by prohibitin. YY1 promoter activity was reduced upon overexpression of prohibitin, while it was enhanced when prohibitin was depleted by small interfering RNA techniques. The repressive effects of prohibitin on the YY1 promoter were mediated through E2F binding sites, as seen by mutational analysis and chromatin immunoprecipitation assays. Further, depletion of E2F1 prevented prohibitin from repressing the YY1 promoter. In contrast with YY1, probibitin overexpression led to enhanced levels of caspase 7, whereas depletion of prohibitin reduced it. Interestingly, the caspase 7 promoter was found to have p53-binding sites and prohibitin activated this promoter through p53. These studies show that prohibitin can have diverse effects on the expression of different genes and the activity of various cellular promoters is affected by prohibitin. Further, it appears very likely that prohibitin carries out many of its cellular functions by affecting the transcription of different acres.