ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein
ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein
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DOI：
10.1038/sj.onc.1209768
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发表时间：
2007-01-04
期刊：
影响因子：
8
通讯作者：
Tsao, Y-P
中科院分区：
文献类型：
--
作者：
Chen, S-L;Lin, S-T;Tsao, Y-P
人乳头瘤病毒16型E5（Human papillomavirus type 16 E5，HPV-16 E5）是一种高度疏水的膜蛋白，具有弱的转化活性，在HPV-16感染的宫颈病变中与ErbB 4受体相关。目前，我们研究了ErbB 4信号通路参与E5转化的机制。首先，我们报道了ErbB 4（JM-b/CYT-1）受体在配体非依赖性和Ras-c-jun氨基末端激酶依赖性途径中激活c-jun基因表达和c-Jun蛋白的Ser 63和Ser 73磷酸化的作用。其次，我们发现HPV-16 E5蛋白可以通过结合ErbB 4的胞外和跨膜结构域与ErbB 4形成复合物（JM-b/CYT-1）。当在细胞中共表达HPV-16 E5和ErbB 4时，与ErbB 4表达细胞相比，E5可以消除ErbB 4诱导的c-Jun蛋白表达和磷酸化导致细胞增殖增加。HPV-16 E5和ErbB 4之间的相互作用为HPV-16 E5转化诱导机制提供了更多的见解。
Human papillomavirus type 16 E5 (HPV-16 E5) is a highly hydrophobic membrane protein with weak-transforming activity, which is associated with ErbB4 receptor in HPV-16-infected cervical lesions. Presently, we investigated the transforming mechanisms of E5 involving ErbB4 signaling. Firstly, we report a role for ErbB4 (JM-b/CYT-1) receptor that activates c-jun gene expression and phosphorylating at Ser63 and Ser73 of the c-Jun protein in ligand-independent and Ras-c-jun NH2-terminal kinase-dependent pathway. Secondly, we show that HPV-16 E5 protein can form a complex with ErbB4 via binding to the extracellular and transmembrane domains of ErbB4 (JM-b/CYT-1). When co-expressing HPV-16 E5 and ErbB4 in cells, E5 can abrogate ErbB4-induced c-Jun protein expression and phosphorylation resulted in increasing cell proliferation compared to ErbB4-expressing cells. The interaction between of HPV-16 E5 and ErbB4 provides more insight into the mechanisms of HPV-16 E5 transformation induction.