Destabilization of TIP60 by Human Papillomavirus E6 Results in Attenuation of TIP60-Dependent Transcriptional Regulation and Apoptotic Pathway
Copyright policy )Destabilization of TIP60 by Human Papillomavirus E6 Results in Attenuation of TIP60-Dependent Transcriptional Regulation and Apoptotic Pathway
The TIP60 tumor suppressor is a histone acetyltransferase involved in transcriptional regulation, checkpoint activation, and p53-directed proapoptotic pathways. We report that human papillomavirus (HPV) E6 destabilizes TIP60 both in vivo and in vitro. TIP60 binds to the HPV major early promoter and acetylates histone H4 to recruit Brd4, a cellular repressor of HPV E6 expression. Both low- and high-risk HPV E6 destabilize TIP60, thereby derepressing their own promoter. Destabilization of TIP60 by HPV E6 also relieves cellular promoters from TIP60-initiated repression and abrogates p53-dependent activation of apoptotic pathway. Degradation of TIP60, therefore, allows low- and high-risk HPV to promote cell proliferation and cell survival.
- University of Alabama at Birmingham United States
- University of Virginia United States
Proteasome Endopeptidase Complex, Transcription, Genetic, Ubiquitin-Protein Ligases, Papillomavirus Infections, Nuclear Proteins, PDZ Domains, Apoptosis, Cell Cycle Proteins, Cell Biology, Oncogene Proteins, Viral, Lysine Acetyltransferase 5, DNA-Binding Proteins, Histones, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Molecular Biology, Proteasome Inhibitors, HeLa Cells, Histone Acetyltransferases, Transcription Factors
Proteasome Endopeptidase Complex, Transcription, Genetic, Ubiquitin-Protein Ligases, Papillomavirus Infections, Nuclear Proteins, PDZ Domains, Apoptosis, Cell Cycle Proteins, Cell Biology, Oncogene Proteins, Viral, Lysine Acetyltransferase 5, DNA-Binding Proteins, Histones, Gene Expression Regulation, Humans, Promoter Regions, Genetic, Molecular Biology, Proteasome Inhibitors, HeLa Cells, Histone Acetyltransferases, Transcription Factors
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