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7151016 
Journal Article 
Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway 
Jha, S; Vande Pol, S; Banerjee, NS; Dutta, AB; Chow, LT; Dutta, A; , 
2010 
1 
Molecular Cell
ISSN: 1097-2765
EISSN: 1097-4164 
CELL PRESS 
CAMBRIDGE 
700-711 
English 
20542002 
WOS:000278950800010 
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.