Kwon Eunjeong, Hayashi Yuko, Otsuki Kyoko, Hirose Fumiko, Nishida Yasuyoshi, Yoo Mi-Ae, Yamaguchi Masamitsu
Division of Biochemistry, Aichi Cancer Center Research Institute, Chikusa, Nagoya 464-8681, Japan.
Biochim Biophys Acta. 2004 Sep 17;1679(3):256-62. doi: 10.1016/j.bbaexp.2004.07.003.
Here we show that Armadillo and Pangolin (dTCF), downstream effectors of the Wingless (Wg) signal transduction pathway, activate transcription of the important DNA replication-related genes encoding Drosophila proliferating cell nuclear antigen (PCNA) and DNA replication-related element-binding factor (DREF). By transient luciferase expression assays and band mobility shift assays, we demonstrated the PCNA gene to be a direct target gene for the Armadillo/Pangolin complex. Using a GAL4-UAS system, stimulation of the PCNA gene by Armadillo/Pangolin was confirmed in adult females. From the published reports of an inhibitory role, we expected that Drosophila CREB-binding protein (dCBP) would interfere with activation. However, effects were only observed with the DREF but not the PCNA gene. In the latter case, as in mammals, dCBP could potentiate Armadillo-mediated activation. These results suggest that first, PCNA and DREF genes are targets of the Armadillo/Pangolin complex and second, dCBP modulates Wg signaling in a gene-specific manner.
我们在此表明,无翅(Wg)信号转导途径的下游效应分子犰狳蛋白和穿山甲蛋白(dTCF)可激活重要的DNA复制相关基因的转录,这些基因编码果蝇增殖细胞核抗原(PCNA)和DNA复制相关元件结合因子(DREF)。通过瞬时荧光素酶表达分析和凝胶迁移率变动分析,我们证明PCNA基因是犰狳蛋白/穿山甲蛋白复合物的直接靶基因。使用GAL4-UAS系统,在成年雌性果蝇中证实了犰狳蛋白/穿山甲蛋白对PCNA基因的刺激作用。根据已发表的关于抑制作用的报道,我们预期果蝇CREB结合蛋白(dCBP)会干扰激活过程。然而,仅在DREF基因上观察到了这种效应,而在PCNA基因上未观察到。在后一种情况下,与哺乳动物一样,dCBP可增强犰狳蛋白介导的激活作用。这些结果表明,首先,PCNA和DREF基因是犰狳蛋白/穿山甲蛋白复合物的靶标;其次,dCBP以基因特异性方式调节Wg信号传导。