The Hippo pathway as a target of the Drosophila DRE/DREF transcriptional regulatory pathway.
The Hippo pathway as a target of the Drosophila DRE/DREF transcriptional regulatory pathway.
复制标题
DOI：
10.1038/srep07196
复制
发表时间：
2014-11-26
影响因子：
4.6
通讯作者：
Yamaguchi M
中科院分区：
文献类型：
--
作者：
Vo N;Horii T;Yanai H;Yoshida H;Yamaguchi M
DRE/DREF转录调控系统已被证明激活具有各种功能的各种基因。在果蝇中，已知Hippo途径通过诱导细胞凋亡和细胞周期停滞来抑制细胞增殖，所述细胞凋亡和细胞周期停滞通过Yorkie（转录共激活因子）的失活来实现。在本研究中，我们发现，减少一半剂量的河马（hpo）基因诱导异位DNA合成的眼光盘，抑制过表达的DREF。在DREF过度表达的果蝇中，hpo基因剂量减少一半可减少细胞凋亡。与这些观察结果一致，DREF的过表达增加了眼盘中hpo和磷酸化Yorkie的水平。有趣的是，DREF的过表达显著降低了diap 1-lacZ报告基因。在培养的S2细胞中的荧光素酶报告基因分析显示，在hpo基因启动子区域中鉴定的两个DRE之一负责S2细胞中的启动子活性。此外，内源性hpo mRNA在DREF敲低的S2细胞中减少，并且用抗DREF抗体进行的染色质免疫沉淀试验证明DREF在体内特异性结合含有DRES的hpo基因启动子区域。总之，这些结果表明DRE/DREF途径是hpo基因转录激活所必需的，以积极控制Hippo途径。
The DRE/DREF transcriptional regulatory system has been demonstrated to activate a wide variety of genes with various functions. In Drosophila, the Hippo pathway is known to suppress cell proliferation by inducing apoptosis and cell cycle arrest through inactivation of Yorkie, a transcription co-activator. In the present study, we found that half dose reduction of the hippo (hpo) gene induces ectopic DNA synthesis in eye discs that is suppressed by overexpression of DREF. Half reduction of the hpo gene dose reduced apoptosis in DREF-overexpressing flies. Consistent with these observations, overexpression of DREF increased the levels of hpo and phosphorylated Yorkie in eye discs. Interestingly, the diap1-lacZ reporter was seen to be significantly decreased by overexpression of DREF. Luciferase reporter assays in cultured S2 cells revealed that one of two DREs identified in the hpo gene promoter region was responsible for promoter activity in S2 cells. Furthermore, endogenous hpo mRNA was reduced in DREF knockdown S2 cells, and chromatin immnunoprecipitation assays with anti-DREF antibodies proved that DREF binds specifically to the hpo gene promoter region containing DREs in vivo. Together, these results indicate that the DRE/DREF pathway is required for transcriptional activation of the hpo gene to positively control Hippo pathways.
登录
查看更多内容
影响因子：
4.6
作者：
Oh, Hyangyee;Irvine, Kenneth D.
通讯作者：
Irvine, Kenneth D.
影响因子：
4.6
作者：
Kango-Singh, M;Nolo, R;Halder, G
通讯作者：
Halder, G
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
1.5
作者：
Kawamori, Akihito;Yamaguchi, Masamitsu
通讯作者：
Yamaguchi, Masamitsu
影响因子：
12.3
作者：
Ohler U;Liao GC;Niemann H;Rubin GM
通讯作者：
Rubin GM