Iftner Thomas, Haedicke-Jarboui Juliane, Wu Shwu-Yuan, Chiang Cheng-Ming
Division of Experimental Virology, Institute for Medical Virology, University Hospital Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.
Division of Experimental Virology, Institute for Medical Virology, University Hospital Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany.
Virus Res. 2017 Mar 2;231:76-82. doi: 10.1016/j.virusres.2016.12.006. Epub 2016 Dec 10.
Bromodomain-containing protein 4 (Brd4) is a cellular chromatin-binding factor and transcriptional regulator that recruits sequence-specific transcription factors and chromatin modulators to control target gene transcription. Papillomaviruses (PVs) have evolved to hijack Brd4's activity in order to create a facilitating environment for the viral life cycle. Brd4, in association with the major viral regulatory protein E2, is involved in multiple steps of the PV life cycle including replication initiation, viral gene transcription, and viral genome segregation and maintenance. Phosphorylation of Brd4, regulated by casein kinase II (CK2) and protein phosphatase 2A (PP2A), is critical for viral gene transcription as well as E1- and E2-dependent origin replication. Thus, pharmacological agents regulating Brd4 phosphorylation and inhibitors blocking phospho-Brd4 functions are promising candidates for therapeutic intervention in treating human papillomavirus (HPV) infections as well as associated disease.
含溴结构域蛋白4（Brd4）是一种细胞染色质结合因子和转录调节因子，它招募序列特异性转录因子和染色质调节剂来控制靶基因转录。乳头瘤病毒（PV）已经进化到劫持Brd4的活性，以便为病毒生命周期创造有利环境。Brd4与主要病毒调节蛋白E2结合，参与PV生命周期的多个步骤，包括复制起始、病毒基因转录以及病毒基因组的分离和维持。由酪蛋白激酶II（CK2）和蛋白磷酸酶2A（PP2A）调节的Brd4磷酸化对于病毒基因转录以及E1和E2依赖的起始复制至关重要。因此，调节Brd4磷酸化的药物制剂和阻断磷酸化Brd4功能的抑制剂是治疗人乳头瘤病毒（HPV）感染以及相关疾病的有前景的治疗干预候选药物。
