The activated notch1 receptor cooperates with α-enolase and MBP-1 in modulating c-myc activity
The activated notch1 receptor cooperates with α-enolase and MBP-1 in modulating c-myc activity
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DOI：
10.1128/mcb.00175-08
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发表时间：
2008-08-01
影响因子：
5.3
通讯作者：
Yeh, Tien-Shun
中科院分区：
文献类型：
--
作者：
Hsu, Kai-Wen;Hsieh, Rong-Hong;Yeh, Tien-Shun
Notch信号通路在促进或抑制肿瘤发生中起着多方面的作用。Notch 1受体胞内结构域（N1 IC）是Notch 1受体的活化形式，可激活c-myc原癌基因。N1 IC和转录因子YY 1的复合物结合到人c-myc启动子上，以CBF 1非依赖性方式增强c-myc表达。在这里，我们证明了N1 IC与c-Myc调节蛋白α-烯醇化酶和c-myc启动子结合蛋白1（MBP-1）相互作用。α-烯醇化酶和MBP-1均以CBF 1非依赖性方式抑制N1 IC增强的c-myc启动子活性。P2 c-myc启动子前的YYI应答元件对于N11 C和α-烯醇化酶或MBP-1调节c-myc是必需的和足够的。此外，N1 IC、YY 1和α-烯醇化酶或MBP-1通过与YY 1反应元件结合而与c-myc启动子结合，而CBF 1不与c-myc启动子结合。NIIC可抑制K562细胞向红系分化。α-烯醇化酶和MBP-1的表达缓解了这种抑制。此外，α-烯醇化酶和MBP-1均通过c-ntyc抑制N1 IC增强的集落形成能力。这些结果表明，激活的Notch 1受体和α-烯醇化酶或MBP-1通过结合c-myc启动子的YY 1反应元件来协同控制c-myc表达，从而调节肿瘤发生。
The Notch signal pathway plays multifaceted roles to promote or suppress tumorigenesis. The Notch1 receptor intracellular domain (N1IC), the activated form of the Notch1 receptor, activates the c-myc protooncogene. The complex of N1IC and transcription factor YY1 binds to the human c-myc promoter to enhance c-myc expression in a CBF1-independent manner. Here we demonstrated that N1IC interacted with the c-Myc-regulating proteins alpha-enolase and c-myc promoter binding protein 1 (MBP-1). Both a-enolase and MBP-1 suppressed the N1IC-enhanced activity of the c-myc promoter in a CBF1-independent manner. The YYI response element in front of the P2 c-myc promoter was essential and sufficient for the modulation of c-myc by N11C and alpha-enolase or MBP-1. Furthermore, N1IC, YY1, and alpha-enolase or MBP-1 but not CBF1 bound to the c-myc promoter through associating with the YY1 response element. Hemin-induced erythroid differentiation was suppressed by NIIC in K562 cells. This suppression was relieved by the expression of alpha-enolase and MBP-1. In addition, both a-enolase and MBP-1 suppressed the N1IC-enhanced colony-forming ability through c-ntyc. These results indicate that the activated Notch1 receptor and alpha-enolase or MBP-1 cooperate in controlling c-myc expression through binding the YY1 response element of the c-myc promoter to regulate tumorigenesis.