Gammoh Noor, Gardiol Daniela, Massimi Paola, Banks Lawrence
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
J Virol. 2009 Feb;83(3):1538-43. doi: 10.1128/JVI.01551-08. Epub 2008 Nov 12.
The regulation of human papillomavirus (HPV) gene expression by the E2 protein is a critical feature of the viral life cycle. Previous studies have shown an important role in transcription for the ubiquitin-proteasome pathway, but its role in HPV gene expression has not been addressed. We now show that HPV E2 requires an active proteasome for its optimal transcriptional activator function. This involves an interaction with the Mdm2 ubiquitin ligase, which together with E2 acts synergistically to activate the HPV type 16 promoter. We also show that HPV E2 recruits Mdm2 onto HPV promoter sequences, providing an explanation for this cooperative activity.
E2蛋白对人乳头瘤病毒（HPV）基因表达的调控是病毒生命周期的一个关键特征。先前的研究表明泛素-蛋白酶体途径在转录中起重要作用，但其在HPV基因表达中的作用尚未得到探讨。我们现在发现HPV E2需要一个活跃的蛋白酶体来实现其最佳转录激活功能。这涉及到与Mdm2泛素连接酶的相互作用，Mdm2与E2协同作用以激活16型HPV启动子。我们还发现HPV E2将Mdm2募集到HPV启动子序列上，这为这种协同活性提供了解释。
