Pfaff S L, Duesberg P H
Department of Molecular Biology, University of California, Berkeley 94720.
J Virol. 1988 Oct;62(10):3703-9. doi: 10.1128/JVI.62.10.3703-3709.1988.
The oncogenic avian retrovirus OK10 has the genetic structure gag-delta pol-myc-delta-env. The myc sequence is transduced from a cellular gene, proto-myc, while gag, pol, and env are essential retrovirus genes. By analogy with other directly oncogenic retroviruses, the specific myc sequence of OK10 is thought to be essential for transforming function. However, unlike the specific sequences of all other transforming retroviruses that encode unique transforming proteins, the myc sequence of OK10 encodes two potential transforming proteins, p58 and p200. p200 is translated from the gag-delta pol-myc region of genomic RNA, while p58 is thought to be translated from the gag leader and the open reading frame of myc via a subgenomic mRNA. In this paper, we ask whether both myc genes of OK10 are autonomous transforming genes. By differentially inactivating the p200 myc gene of OK10 provirus in vitro and analyzing transforming function in quail embryo cells, it was found that mutants expressing only p58 transformed like wild-type OK10. Further, it was shown that p58 with and without the gag leader had transforming function and that p58 of wild-type OK10 is initiated from the gag leader. Mutants expressing only p200 were also transforming but less efficiently than mutants that express only p58. A mutant OK10 virus in which the native frameshift of retroviruses between gag and pol was deleted expressed a shortened p200 (delta p200). Although this virus expressed more delta p200 than wild-type OK10 did, it transformed cells less efficiently. It follows that OK10 expresses two autonomous transforming genes, which is unique among retroviruses with onc genes.
致癌性禽逆转录病毒OK10具有gag-δ pol-myc-δ-env的基因结构。myc序列是从细胞基因原癌基因myc转导而来的，而gag、pol和env是逆转录病毒的必需基因。与其他直接致癌的逆转录病毒类似，OK10的特定myc序列被认为对转化功能至关重要。然而，与所有其他编码独特转化蛋白的转化逆转录病毒的特定序列不同，OK10的myc序列编码两种潜在的转化蛋白，p58和p200。p200从基因组RNA的gag-δ pol-myc区域翻译而来，而p58被认为是通过亚基因组mRNA从gag前导序列和myc的开放阅读框翻译而来。在本文中，我们探讨OK10的两个myc基因是否都是自主转化基因。通过在体外差异失活OK10前病毒的p200 myc基因并分析鹌鹑胚胎细胞中的转化功能，发现仅表达p58的突变体与野生型OK10一样具有转化能力。此外，研究表明，有无gag前导序列的p58都具有转化功能，且野生型OK10的p58是从gag前导序列起始的。仅表达p200的突变体也具有转化能力，但效率低于仅表达p58的突变体。一种缺失了逆转录病毒gag和pol之间天然移码的突变OK10病毒表达一种缩短的p200（δ p200）。尽管这种病毒表达的δ p200比野生型OK10更多，但它转化细胞的效率更低。由此可见，OK10表达两个自主转化基因，这在具有癌基因的逆转录病毒中是独一无二的。
