人乳头瘤病毒16型E2反式激活结构域的靶向诱变揭示了可分离的转录激活和DNA复制功能。
Targeted mutagenesis of the human papillomavirus type 16 E2 transactivation domain reveals separable transcriptional activation and DNA replication functions.
作者信息
Sakai H, Yasugi T, Benson J D, Dowhanick J J, Howley P M
机构信息
Department of Pathology, Harvard Medical School, Boston, Massachusetts, 02115, USA.
出版信息
J Virol. 1996 Mar;70(3):1602-11. doi: 10.1128/JVI.70.3.1602-1611.1996.
Abstract
The E2 gene products of papillomavirus play key roles in viral replication, both as regulators of viral transcription and as auxiliary factors that act with E1 in viral DNA replication. We have carried out a detailed structure-function analysis of conserved amino acids within the N-terminal domain of the human papillomavirus type 16 (HPV16) E2 protein. These mutants were tested for their transcriptional activation activities as well as transient DNA replication and E1 binding activities. Analysis of the stably expressed mutants revealed that the transcriptional activation and replication activities of HPV16 E2 could be dissociated. The 173A mutant was defective for the transcriptional activation function but retained wild-type DNA replication activity, whereas the E39A mutant wild-type transcriptional activation function but was defective in transient DNA replication assays. The E39A mutant was also defective for HPV16 E1 binding in vitro, suggesting that the ability of E2 protein to form a complex with E1 appears to be essential for its function as an auxiliary replication factor.
摘要
乳头瘤病毒的E2基因产物在病毒复制中起关键作用，既是病毒转录的调节因子，也是在病毒DNA复制中与E1共同起作用的辅助因子。我们对人乳头瘤病毒16型（HPV16）E2蛋白N端结构域内的保守氨基酸进行了详细的结构-功能分析。对这些突变体进行了转录激活活性、瞬时DNA复制和E1结合活性的检测。对稳定表达的突变体的分析表明，HPV16 E2的转录激活和复制活性可以分离。173A突变体的转录激活功能有缺陷，但保留了野生型DNA复制活性，而E39A突变体具有野生型转录激活功能，但在瞬时DNA复制试验中有缺陷。E39A突变体在体外与HPV16 E1的结合也有缺陷，这表明E2蛋白与E1形成复合物的能力似乎对其作为辅助复制因子的功能至关重要。
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