Inhibition of E2 binding to Brd4 enhances viral genome loss and phenotypic reversion of bovine papillomavirus-transformed cells.
The bovine papillomavirus E2 protein tethers the viral genomes to mitotic chromosomes in dividing cells through binding to the C-terminal domain (CTD) of Brd4. Expression of the Brd4-CTD competes the binding of E2 to endogenous Brd4 in cells. Here we extend our previous study that identified Brd4 as the E2 mitotic chromosome receptor to show that Brd4-CTD expression released the viral DNA from mitotic chromosomes in BPV-1 transformed cells. Furthermore, stable expression of Brd4-CTD enhanced the frequency of morphological reversion of BPV-1 transformed C127 cells resulting in the complete elimination of the viral DNA in the resulting flat revertants.
You
Jianxin
J
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Schweiger
Michal-Ruth
MR
Howley
Peter M
PM
D000818:Animals; D001665:Binding Sites; D052688:Bovine papillomavirus 1 / Q000737:chemistry*; D018797:Cell Cycle Proteins; D002472:Cell Transformation, Viral / Q000502:physiology*; D016679:Genome, Viral / Q000502:physiology*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D010641:Phenotype; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; C441289:BRD4 protein, human; D000092468:Bromodomain Containing Proteins