Aoki M, Vogt P K
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC-239, La Jolla, CA 92037, USA.
Curr Top Microbiol Immunol. 2004;279:321-38. doi: 10.1007/978-3-642-18930-2_19.
Retroviruses have recruited the catalytic subunit of PI 3-kinase and its downstream target, Akt, as oncogenes. These viruses cause tumors in animals and induce oncogenic transformation in cell culture. The oncogenicity of these viruses is specifically inhibited by rapamycin; retroviruses carrying other oncogenes are insensitive to this macrolide antibiotic. Rapamycin is an inhibitor of the TOR (target of rapamycin) kinase whose downstream targets include p70 S6 kinase and the negative regulator of translation initiation 4E-BP. Emerging evidence suggests that the TOR signals transmitted to the translational machinery are essential for oncogenic transformation by the PI 3-kinase pathway.
逆转录病毒已将磷脂酰肌醇-3激酶（PI 3-kinase）的催化亚基及其下游靶点Akt招募为癌基因。这些病毒可在动物体内引发肿瘤，并在细胞培养中诱导致癌转化。这些病毒的致癌性可被雷帕霉素特异性抑制；携带其他癌基因的逆转录病毒对这种大环内酯类抗生素不敏感。雷帕霉素是雷帕霉素靶蛋白（TOR）激酶的抑制剂，其下游靶点包括p70 S6激酶和翻译起始负调节因子4E-BP。新出现的证据表明，通过PI 3-激酶途径传递到翻译机制的TOR信号对于致癌转化至关重要。
