p73 interacts with c-Myc to regulate Y-box-binding protein-1 expression
p73 interacts with c-Myc to regulate Y-box-binding protein-1 expression
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DOI：
10.1074/jbc.m200266200
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发表时间：
2002-08-30
影响因子：
4.8
通讯作者：
Kohno, K
中科院分区：
文献类型：
--
作者：
Uramoto, H;Izumi, H;Kohno, K
YB-1是冷休克结构域家族的一员，对DNA损伤和细胞增殖的信号传导很重要。YB-1由DNA损伤诱导，也能识别顺铂修饰的DNA。在这项研究中，我们观察到在人类癌细胞系KB细胞中，YB-1 mRNA的稳态水平在顺铂暴露的反应中增加了6倍。我们从共转染实验中提出证据，证明c-Myc和p73在YB-1启动子的转激活中起关键作用。p73在表达c-Myc的Saos-2细胞中激活了YB-1启动子，而在缺乏c-Myc的HO15.19细胞中则没有。反过来，c-Myc反激活了一个完整的YB-1启动子，但没有激活带有突变E-box的YB-1启动子，这表明E-box对于启动子对顺铂的反应是必要的。我们还发现p73在体外和体内与c-Myc相互作用。利用缺失突变体，我们发现p73的dna结合域和c-Myc的c端区域是相互作用所必需的。此外，p73刺激Max与c-Myc的相互作用，促进c-Myc-Max复合物与目标DNA的结合。我们的数据表明，p73通过促进c-Myc-Max复合物向E-box的募集来刺激YB-1启动子的转录。
YB-1 is a member of the cold shock domain family of proteins that is important for signaling DNA damage and cell proliferation. YB-1 is induced by DNA damage and can also recognize cisplatin-modified DNA. In this study we observed a 6-fold increase in the steady-state level of YB-1 mRNA in response to cisplatin exposure in cells of the human cancer cell line KB. We present evidence from cotransfection experiments for a critical role of c-Myc and p73 in the transactivation of the YB-1 promoter. p73 transactivated the YB-1 promoter in experiments with Saos-2 cells, which express c-Myc, but not with HO15.19 cells, which lack c-Myc. In turn, c-Myc transactivated an intact YB-1 promoter but not a YB-1 promoter with a mutant E-box, indicating that the E-box is necessary for the response of the promoter to cisplatin. We also found that p73 interacts with c-Myc in vitro and in vivo. Using deletion mutants we showed that the DNA-binding domain of p,73 and the C-terminal region of c-Myc are required for the interaction. Furthermore, p73 stimulated the interaction of Max with c-Myc and promoted binding of the c-Myc-Max complex to its target DNA. Our data suggest that p73 stimulates the transcription of the YB-1 promoter by enhancing recruitment of the c-Myc-Max complex to the E-box.